LL-37 (Cathelicidin)
LL-37 (cathelicidin) — the double-edged antimicrobial peptide: healer, and driver of rosacea/psoriasis

Class: peptide
Synonyms: LL-37
cathelicidin (the human cathelicidin)
the C-terminal active fragment of hCAP18 (gene CAMP)
Function tags: (defensive:) antimicrobial
wound healing
angiogenesis
(pathological when dysregulated:) rosacea / psoriasis / lupus inflammation
(gray-market pitch:) healing / anti-infective / skin
Overall evidence grade: A
WADA prohibited: no
Last updated: 2026-07-13

In brief: LL-37 is the body's own broad-spectrum antimicrobial peptide — the only human cathelicidin — a 37-amino-acid innate-immune effector made by skin and immune cells, switched on by vitamin D and injury, and activated by protease cleavage. It genuinely kills microbes (by disrupting their membranes) and supports wound healing and angiogenesis. But its defining feature is a dual role: it's also an "alarmin," and when its expression or processing goes wrong, it becomes a driver of inflammatory and autoimmune disease — it generates the inflammatory fragments of rosacea, breaks tolerance to self-DNA in psoriasis (via TLR9), and feeds lupus. That's the paradox for a register: LL-37 is sold as a healing/antimicrobial peptide, but its largest, most rigorous evidence base is about how it causes skin disease when dysregulated. As an exogenous therapeutic it's preclinical with no approvals, and administering a pro-inflammatory alarmin — particularly to anyone prone to rosacea or psoriasis — could plausibly do the opposite of healing. A fascinating, important molecule; a genuinely double-edged one; not a validated therapy.

## Identity the **only human cathelicidin** — a **37-amino-acid, cationic, amphipathic α-helical peptide** that is a core effector of **innate immunity**. It's produced as an inactive precursor (**hCAP18**) by **keratinocytes, neutrophils** and other cells, then **cleaved by proteases (kallikreins KLK5/KLK7)** into the active **LL-37**. Its production is **induced by vitamin D** (UV light → vitamin D → cathelicidin — one reason facial skin is a hotspot) and by an alternative **ER-stress pathway**. It sits in the skin's **chemical barrier** — the first line of defense against microbes. ## Mechanism (as proposed) LL-37 is **cationic and amphipathic**, so it's drawn to **negatively-charged microbial membranes**, which it **inserts into and disrupts**, killing bacteria rapidly and broadly (its **antimicrobial** face). But the *same* peptide is a **host immunomodulator/"alarmin"**: it **chemoattracts** immune cells, promotes **angiogenesis** and wound repair, and — critically — **binds host nucleic acids (self-DNA/RNA)** and ferries them into immune cells, where they **activate Toll-like receptors (notably TLR9)**. In healthy skin this is controlled; when **cathelicidin is over-expressed (psoriasis)** or **mis-processed into inflammatory fragments (rosacea)** or released in **NETs (lupus)**, it **breaks immune tolerance and ignites chronic inflammation/autoimmunity**. So LL-37's healing and harming functions are **two faces of one molecule** — which is exactly why exogenous use is not a simple "healing peptide" proposition.

Evidence grades by outcome:
outcome: Endogenous antimicrobial defense
grade: A
base: Extensive: potent broad-spectrum membrane-disrupting killing; surges in wounds
caveat: This grades LL-37's natural role — NOT a demonstrated benefit of taking exogenous LL-37
outcome: Exogenous wound healing / antimicrobial therapy (the marketed use)
grade: D
base: Preclinical / early; angiogenic & pro-healing in models
caveat: No approved product; no human trials establishing efficacy or safety of exogenous use
outcome: Role in rosacea (as a cause)
grade: A
base: Strong: abnormal processing → pro-inflammatory fragments → erythema/telangiectasia
caveat: This is evidence it drives disease — a reason for caution, not a therapeutic credential
outcome: Role in psoriasis / lupus (as a cause)
grade: A
base: Strong: LL-37+self-DNA→TLR9→break self-tolerance; T-cell autoantigen; NET/IFN in SLE
caveat: Again: robust evidence of harm/pathogenic role, underscoring the risk of exogenous use
outcome: Safety of exogenous administration
base: Not established in humans
caveat: It's a pro-inflammatory alarmin; plausible to trigger/worsen inflammatory-autoimmune skin disease; contraindicated intuition for rosacea/psoriasis-prone users

Legal status:
region: EU
status: not an approved drug
note: not an approved drug; investigational. Not an approved cosmetic ingredient (an injectable pro-inflammatory alarmin is not a topical cosmetic). No compounding pathway.

Cosmetic claims:

Note: The double-edged sword of innate immunity — a natural antibiotic that, dysregulated, drives inflammatory disease. LL-37 is unusual in this register: it's sold as a healing/antimicrobial peptide, yet its largest and strongest evidence base is about its role in causing skin disease (rosacea, psoriasis, lupus). Three threads: (1) it's the body's own broad-spectrum antimicrobial peptide and a genuine innate-immune effector; (2) it has a "dual role" — antimicrobial and an "alarmin" that, when mis-processed or over-expressed, triggers inflammation, redness, and autoimmunity; (3) that means exogenous LL-37, marketed as healing, can plausibly feed the very inflammatory conditions its biology is famous for — the opposite of the intended pitch.
Status note: watch: engineered LL-37 analogs/fragments that dissociate antimicrobial from pro-inflammatory activity — the field's key therapeutic goal

Sources:
Reinholz M, Ruzicka T, Schauber J. Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease. Ann Dermatol. 2012 (dual role; rosacea/psoriasis/AD; vitamin D & ER-stress induction).
Lande R, et al. Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self-DNA. (LL-37 + self-DNA → TLR9/pDC); LL-37 as psoriasis T-cell autoantigen.
Yamasaki K, Di Nardo A, Gallo RL, et al. — cathelicidin processing (KLK5/KLK7) and pro-inflammatory fragments in rosacea.
Reviews: innate immunity & cathelicidin in inflammatory skin disease (PMC3904447); LL-37 as a "double-edged sword" (host defense vs disease). (Exogenous therapeutic use preclinical; no human approvals as of 2026.)