LL-37 (with Bacteriostatic Water)

LL-37 is the C-terminal 37-residue cationic alpha-helical peptide derived from the only cathelicidin gene in the human genome — the CAMP gene encoding the human cathelicidin antimicrobial protein (hCAP18). The name "LL-37" derives from the two N-terminal leucines and the 37-residue length of the active processed peptide. The peptide was first identified and characterized in the 1990s by groups including Robert Lehrer at UCLA and Birgitta Agerberth at the Karolinska Institute in Stockholm, in the context of the broader cathelicidin family characterization that had begun with the bovine and porcine cathelicidins identified earlier in that decade.

LL-37 occupies a central position in human innate-immune biology. It is expressed by neutrophils (where it is stored in the secondary granules and released during neutrophil activation), by epithelial cells across multiple tissue interfaces with the external environment (skin keratinocytes, respiratory and intestinal epithelial cells, urogenital epithelial cells), and by mast cells and certain other immune cell types. Its biological functions extend well beyond the original antimicrobial-peptide framing: published research over the past three decades has characterized LL-37 as having direct antimicrobial activity against a broad spectrum of bacteria, fungi, and certain viruses, but also as having a substantial repertoire of immunomodulatory effects — chemotactic activity for neutrophils, monocytes, T cells, and mast cells; effects on dendritic-cell maturation; modulation of cytokine production by multiple cell types; effects on wound-healing and epithelial-repair processes; and broader integration with the regulation of inflammation that has reframed the peptide as a multifunctional component of the innate-immune response rather than purely an antimicrobial.

This page is an educational reference for readers who want a careful, plain-English explanation of what LL-37 actually is, where it sits in the human cathelicidin and broader antimicrobial-peptide story, what the published research describes about its mechanisms and effects across the antimicrobial and immunomodulatory domains, and where it fits in the broader landscape of innate-immunity research peptides. It is not a medical guide, does not describe any therapy or antimicrobial protocol, and makes no claims about effects in people who acquire the compound for research purposes. LL-37 supplied as a research peptide is intended for laboratory and analytical work only.

LL-37 is a 37-residue linear cationic peptide with the sequence LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES. The molecular formula is C205H340N60O53, with a molecular weight of approximately 4493 daltons. The peptide is amphipathic — when folded into its biologically active alpha-helical conformation, it presents a hydrophobic face on one side of the helix (contributed by the leucines, isoleucines, valines, and phenylalanines) and a cationic hydrophilic face on the other side (contributed by the multiple lysines and arginines, which give the peptide a net charge of approximately +6 at physiological pH). This amphipathic-helical architecture is the structural foundation for the membrane-interaction biology that underlies LL-37's direct antimicrobial activity.

The peptide is produced in vivo by proteolytic processing of a larger precursor. The CAMP gene encodes a 170-residue precursor protein called hCAP18 (human cationic antimicrobial protein, 18 kDa) consisting of an N-terminal signal peptide, a conserved cathelin pro-region of approximately 100 residues (homologous to the calf-cathepsin-L inhibitor "cathelin" from which the cathelicidin family takes its name), and the C-terminal cationic antimicrobial domain that becomes LL-37 upon processing. The mature hCAP18 is stored in the secondary granules of neutrophils and in the granules of various other cell types, and the C-terminal LL-37 domain is liberated by proteolytic cleavage carried out predominantly by proteinase 3 in neutrophils and by kallikrein-5 (KLK5) and other tissue kallikreins in keratinocytes and other epithelial cells.

The biological functions of LL-37 are dual. The first is the direct antimicrobial activity originally characterized — the peptide kills a broad spectrum of bacteria (both Gram-positive and Gram-negative), fungi, certain enveloped viruses, and some parasites through the membrane-disrupting mechanism shared by many cationic amphipathic antimicrobial peptides. The second is a substantial repertoire of immunomodulatory effects characterized in the more recent research literature — chemotactic activity for neutrophils, monocytes, T cells, and mast cells (signaling primarily through the formyl-peptide receptor 2, FPR2/ALX); effects on dendritic-cell maturation and on dendritic-cell-mediated T-cell activation; modulation of cytokine production by multiple cell types; effects on epithelial-repair and wound-healing processes; and broader regulation of inflammation.

It is worth being specific about what LL-37 is not. It is not a defensin — the defensins (α-defensins, β-defensins, θ-defensins) are a structurally distinct family of cationic antimicrobial peptides with disulfide-stabilized β-sheet architectures, while LL-37 is an unstructured-in-water peptide that adopts an amphipathic α-helical conformation upon membrane interaction. It is not a synthetic antibiotic — although it has direct antimicrobial activity, the mechanism (membrane disruption) and the structural class (cationic amphipathic peptide) are distinct from the small-molecule antibiotics that dominate clinical antimicrobial therapy. And it is not an approved medicine in any major international regulatory jurisdiction; the research-peptide form is supplied for laboratory and analytical use only.

The history of LL-37 is part of the broader history of cationic antimicrobial peptide research that emerged as a distinct field in the 1980s and 1990s. The first cathelicidins were identified in cattle and pigs in the early 1990s — the bovine indolicidin and the porcine PR-39 and protegrins were among the foundational members of the family — and the structural pattern of an N-terminal conserved cathelin pro-region followed by a variable C-terminal antimicrobial domain became the defining feature of the cathelicidin family.

LL-37 was identified in the mid-1990s by independent work from groups including Birgitta Agerberth and Hans Jörnvall at the Karolinska Institute and Robert Lehrer at UCLA. The CAMP gene was characterized as the only cathelicidin gene in the human genome (a striking finding given the multiple cathelicidins present in many other mammalian genomes), and the C-terminal 37-residue cationic peptide was characterized as the processed active form. The name "LL-37" was assigned based on the two N-terminal leucines and the 37-residue length.

Through the late 1990s and early 2000s, the published LL-37 literature focused predominantly on the direct antimicrobial activity — characterization of activity spectra against various bacterial, fungal, and viral pathogens; characterization of the membrane-disruption mechanism through model-membrane studies and through biophysical characterization of the peptide-membrane interaction; structure-activity studies using truncated and modified LL-37 analogs; and characterization of how the peptide's activity is modulated by physiological factors including ionic strength, calcium concentration, and the presence of various biological fluids and matrices.

The mid-2000s saw a substantial expansion of the LL-37 literature into the immunomodulatory domain. The recognition that the peptide had chemotactic activity for neutrophils and other cell types through the formyl-peptide receptor 2 (FPR2/ALX), the characterization of effects on dendritic-cell biology and on the integration of innate and adaptive immunity, and the broader characterization of LL-37 as a multifunctional immunomodulator rather than purely an antimicrobial reframed the conversation about the peptide and its role in human innate-immune biology. Niels Borregaard and his collaborators in Copenhagen contributed significantly to the characterization of hCAP18/LL-37 biology in neutrophils, and Richard Gallo's group at UCSD contributed extensively to the characterization of LL-37 biology in skin.

The 2010s and 2020s have seen continuing research on LL-37 in multiple domains: in skin biology (where the peptide has been characterized in the context of conditions including rosacea, atopic dermatitis, and acne, with the kallikrein-mediated processing of hCAP18 and the consequent generation of various LL-37 fragments emerging as a particular focus); in respiratory and mucosal biology; in wound-healing research; and in the broader integration with the innate-immune-system landscape. The continuing development of LL-37 analogs and mimetics as antimicrobial-resistance research tools has been one of the active translational areas, though as of this writing no LL-37-based therapy has been approved in major regulatory jurisdictions.

The science of LL-37 is organized around three connected areas: the membrane-disruption mechanism underlying the direct antimicrobial activity, the receptor-mediated immunomodulatory effects, and the regulation of hCAP18/LL-37 expression and processing in different tissue contexts.

• 37-residue cationic alpha-helical peptide; MW approximately 4493 Da; the only cathelicidin in the human genome.
• Derived from the hCAP18 precursor (CAMP gene); released by proteinase 3 (in neutrophils) and kallikrein-5 (in epithelia) processing.
• Direct antimicrobial activity against broad spectrum of bacteria, fungi, and some viruses through membrane-disruption mechanism.
• Substantial immunomodulatory effects through FPR2/ALX receptor: chemotaxis for neutrophils/monocytes/T cells/mast cells; effects on dendritic cells; cytokine modulation.
• Expression induced by vitamin D signaling through a vitamin-D-response element in the CAMP gene promoter.

Structurally, LL-37 is a linear 37-residue peptide with the sequence LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES. The molecular formula is C205H340N60O53, with a molecular weight of approximately 4493 daltons. The peptide is in the all-L-amino-acid configuration, has no disulfide bonds (no cysteine residues in the sequence), no covalent modifications beyond the standard amide-bond backbone, and a free C-terminal carboxylate (no C-terminal amidation, distinguishing it from many other cationic antimicrobial peptides that are amidated).

The amino-acid composition gives the peptide a net charge of approximately +6 at physiological pH from the multiple lysines (six positions: K8, K10, K12, K15, K18, and K25) and arginines (five positions: R7, R19, R23, R29, and R34), partly compensated by the aspartates (positions 4 and 26) and the glutamates (positions 11, 16, and the C-terminal E37). The hydrophobic content is substantial — multiple leucines, isoleucines, valines, and phenylalanines — and these residues cluster on one face of the alpha-helical conformation that the peptide adopts upon membrane interaction.

The peptide is largely unstructured in aqueous solution at physiological ionic strength but adopts an amphipathic α-helical conformation upon binding to anionic membrane surfaces or to certain other anionic biological molecules. This conformational transition — from disordered in water to α-helical at membranes — is the structural foundation for both the direct antimicrobial activity and many of the receptor-mediated immunomodulatory effects.

The aromatic content includes the two phenylalanines (F5 and F6 near the N-terminus, contributing to UV absorbance), with no tryptophan and no tyrosine. The 280 nm UV absorbance is therefore modest compared to peptides with tryptophan, and concentration determination for LL-37 research preparations is typically done by alternative approaches such as quantitative amino acid analysis or mass-based weighing.

LL-37 is studied across an unusually broad range of laboratory contexts in innate immunology, antimicrobial-peptide biology, and related fields.

In antimicrobial-research contexts, LL-37 is used in characterization of activity spectra against various bacterial, fungal, and viral pathogens; in studies of the membrane-disruption mechanism through model-membrane systems and through biophysical characterization of the peptide-membrane interaction; in structure-activity studies using truncated and modified LL-37 analogs and various peptidomimetic compounds; and in investigation of the modulation of activity by physiological factors including ionic strength, calcium concentration, and various biological matrix components.

In innate-immunity and immunomodulation research, LL-37 is used in characterization of chemotactic activity for various immune cell types (neutrophils, monocytes, T cells, mast cells) through FPR2/ALX-mediated signaling; in characterization of effects on dendritic-cell maturation and on the integration of innate and adaptive immunity; in characterization of effects on cytokine production by macrophages, dendritic cells, and other cell types; in characterization of effects on the broader Toll-like-receptor signaling landscape (including the LL-37-DNA complex effects on TLR9 that have been characterized in the psoriasis-research context); and in the broader integration with the innate-immune-system landscape.

In wound-healing and skin-biology research, LL-37 is used in characterization of effects on keratinocyte migration and proliferation, on dermal-fibroblast biology, on angiogenesis, and on broader integration with the wound-healing response. The skin-research applications also include characterization of LL-37 biology in the context of inflammatory skin conditions (rosacea, atopic dermatitis, acne, psoriasis), where the kallikrein-mediated processing of hCAP18 and the generation of various LL-37-related fragments have been characterized as relevant to disease pathophysiology.

In respiratory and mucosal-immunology research, LL-37 is studied in characterization of effects on airway-epithelial cells, on mucosal-immune responses, and on host defense against respiratory pathogens. The mucosal-research applications include both upper-airway (nasal, oral) and lower-airway (bronchial, pulmonary) contexts.

In vitamin D immunology research, the regulatory connection between vitamin D signaling and CAMP expression has framed continuing research on the integration of vitamin D status with innate-immune function. This research context has expanded substantially over the past two decades and connects LL-37 biology to the broader vitamin D research field.

Across all of these contexts, the research applications are laboratory and analytical in nature. The research-peptide supply of LL-37 is intended for laboratory work only and does not include any clinical, therapeutic, or antimicrobial-treatment context.

LL-37 sits within the broader family of cationic antimicrobial peptides and within the cathelicidin family specifically, with distinctive comparators across the antimicrobial-peptide landscape.

LL-37 is a 37-residue cationic alpha-helical peptide of approximately 4493 daltons — the C-terminal active fragment of hCAP18, the only cathelicidin in the human genome. The peptide is expressed by neutrophils (where the precursor is stored in secondary granules and released upon activation), by epithelial cells across multiple tissue interfaces with the external environment (skin keratinocytes, respiratory and intestinal epithelia, urogenital epithelia), and by mast cells and certain other immune cell types. Its release as the active LL-37 form is carried out by proteinase 3 in neutrophils and by kallikrein-5 and other tissue kallikreins in epithelial contexts.

The biological functions of LL-37 extend well beyond the original antimicrobial-peptide framing. The peptide has direct antimicrobial activity against a broad spectrum of bacteria, fungi, and certain viruses through the membrane-disruption mechanism shared by many cationic amphipathic antimicrobial peptides. It also has a substantial repertoire of immunomodulatory effects mediated principally through the formyl-peptide receptor 2 (FPR2/ALX) — chemotactic activity for neutrophils, monocytes, T cells, and mast cells; effects on dendritic-cell maturation and on the integration of innate and adaptive immunity; modulation of cytokine production by multiple cell types; effects on wound-healing and epithelial-repair processes; and broader integration with the regulation of inflammation. These immunomodulatory effects have reframed LL-37 as a multifunctional component of the innate-immune response rather than purely an antimicrobial.

The regulation of LL-37 expression by 1,25-dihydroxyvitamin D3 signaling through a vitamin-D-response element in the CAMP promoter has linked the peptide's biology to the broader vitamin D immunology field. The connections to specific disease contexts (the LL-37-DNA complex contribution to psoriasis pathophysiology characterized by the Gilliet, Lande, and colleagues' work; the kallikrein-mediated alternative processing relevant to rosacea characterized by the Gallo group; and others) have framed continuing research on LL-37 in skin biology and in inflammatory-disease pathophysiology.

LL-37 is not approved as a medicine in major international regulatory jurisdictions. The research-peptide form is supplied for laboratory and analytical use only, and educational discussion should remain within that framing rather than drift into therapeutic claims about antimicrobial or wound-healing treatment.

For students, researchers, and curious readers approaching LL-37 for the first time, the most accurate framing is of the single human cathelicidin peptide, of a multifunctional innate-immune peptide combining direct antimicrobial activity with substantial immunomodulatory effects, of a peptide whose biology is integrated with vitamin D signaling and with multiple specific disease-pathophysiology contexts, and of a research peptide widely used as a tool for characterizing the broader cathelicidin and antimicrobial-peptide landscape.