LL-37

Molecular identity

Sequence

Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys-Glu-Lys-Ile-Gly-Lys-Glu-Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg-Asn-Leu-Val-Pro-Arg-Thr-Glu-Ser

Formula

C205H340N60O53

Molecular weight

4493 g/mol

CAS

154947-66-7

PubChem CID

16198951

What it acts on

• The variable C-terminal cathelicidin domain — the reviews assign both the antimicrobial and the immunomodulatory activity to this region rather than to the conserved cathelin-homologous N-terminal pre-pro region, and report direct activity across bacteria, fungi, viruses and parasites.
• Human immune receptors contacted by the LL-37 domain and its sub-fragments SK-24, IV-20 and FK-13 — the 2023 review proposes these fragments as the units that actually engage receptors, while stating that the molecular basis of the induced immune response is still unclear.
• Chemotactic and immunomodulatory signalling traced through the immunological, respiratory, gastrointestinal and cutaneous systems — the 2016 review describes potent chemotaxis running alongside the direct antimicrobial action and maps cathelicidin-dependent pathways onto specific diseases.
• The pro-inflammatory cathelicidin–inflammasome axis in skin — the rosacea review places this pathway at the centre of a chronic inflammatory dermatosis, so in that literature the same peptide reads as a driver of inflammation and not only as a defence molecule.
• Proteolytic degradation of the native sequence — the 2025 modification review lists low proteolytic stability alongside cytotoxicity and high production costs among the limitations that hinder clinical application, and gives particular attention to truncated and retro-analogues with increased proteolytic resistance.

What the studies report

Each item below summarises the paper it is numbered to, written from that paper's own abstract. The badge says how the evidence was produced.

1. 1.
   reviewPeptides (2023)

   A 2023 review in Peptides examining the LL-37 domain across cathelicidins from mammals, fish, birds, amphibians and reptiles. It sets out the family architecture — a conserved cathelin-homologous N-terminal pre-pro region and a variable C-terminal domain carrying the antimicrobial and immunomodulatory activity — and suggests that the LL-37 domain together with its SK-24, IV-20 and FK-13 fragments may be what interacts with receptors in humans. The authors state outright that the molecular basis by which cathelicidins induce an immune response is still unclear, so the fragment account is offered as a clue for further work, not as a demonstrated mechanism.

2. 2.
   reviewPharmacol Rep (2016)

   A 2016 pharmacology review of the sole human cathelicidin, covering four systems — immunological, respiratory, gastrointestinal and cutaneous — and relating cathelicidin-dependent molecular pathways to specific diseases. It reports broad-spectrum antibiotic action together with potent chemotactic and immunomodulatory properties, in the context of antimicrobial peptides distributed mainly in mucus layers, where they prevent colonisation by pathogens. It is a narrative review rather than a systematic one, and its own conclusion is a call for further investigation and development, not a statement that the peptide has been shown to work clinically.

3. 3.
   reviewInt J Mol Sci (2025)

   A 2025 review of chemical and structural modification strategies applied to LL-37. It names the obstacles that keep the native peptide out of clinical use — low proteolytic stability, cytotoxicity and high production costs — and surveys truncated and retro-analogues that preserve or improve activity while showing reduced toxicity and greater proteolytic resistance, alongside nanoscale delivery systems intended to prolong half-life and mitigate cytotoxic effects. The authors state that peptide design, cost-effective production and long-term safety and efficacy all still require optimisation and validation, which places the analogue work firmly at candidate stage.

4. 4.
   reviewJ Cutan Med Surg (2024)

   A 2024 dermatology review of rosacea pathogenesis, relevant here because it is where cathelicidin biology is read in the opposite direction. It places pro-inflammatory pathways involving cathelicidins and inflammasome complexes at the centre of a chronic inflammatory skin condition for which there is no cure, and suggests that established and emerging treatments may owe their efficacy to acting on those same pathways, with common triggers modulating them in a complex manner. The review itself calls the pathogenesis likely multifactorial, with genetic and environmental contributions, so the cathelicidin account is one strand of a working hypothesis rather than a settled mechanism.

Used in research on