Discovery & the cathelicidin family

• How LL-37 is cut from hCAP-18 and why it is the only human cathelicidin
• How the helix disrupts membranes, and what the sources do and do not measure
• How LL-37 steers immune cells through FPR2 and drives wound repair
• Where the double-edged risks (cytotoxicity, inflammation, cancer) really sit

1. 01 Discovery & the cathelicidin family The one antimicrobial peptide your own cells make free
2. 02 Structure: the amphipathic helix How 37 residues fold into a membrane-breaking tool paid
3. 03 Vitamin D induction & regulation What turns the LL-37 gene up and down paid
4. 04 Antimicrobial mechanism How a peptide breaks a bacterium open paid
5. 05 Immunomodulation & chemotaxis The peptide that tells immune cells where to go paid
6. 06 Wound healing & the clinical record From clearing infection to rebuilding skin paid
7. 07 Antiviral defense & LPS neutralization Against viruses and against the poison of dead bacteria paid
8. 08 Disease associations & the double edge When a protector turns provocateur paid
9. 09 Therapeutic development & delivery Why a promising peptide is so hard to turn into a drug paid
10. 10 Dosing & Administration How LL-37 is handled in research, read critically paid
11. 11 Safety & the double-edged risks What we know about LL-37 risks, and what we do not paid
12. 12 Final Exam & Certification Pass the final exam to earn your certificate of completion. Exam

LL-37 was not invented in a lab; it was discovered inside us. Researchers tracing the cathelicidin family found peptides built on a shared precursor design across many vertebrates, each species carrying its own versions, while humans express just one gene, CAMP. Its product, hCAP-18, is cut by proteases to free the active 37-residue peptide. The timeline below marks how a curiosity of innate immunity became one of the most studied human antimicrobial peptides.

Read the timeline as a widening of scope. LL-37 started as a membrane-punching antibiotic, then turned out to steer immune traffic, heal tissue, and, less happily, feed some autoimmune and tumor processes. That expanding, occasionally contradictory role is exactly why a careful course is worth your time.

Being the only cathelicidin in the human genome is what makes LL-37 unusually important: it has to cover antibacterial, antiviral, and immune-signaling duties by itself. The cathelicidin family reaches across vertebrates, but the peptides are species-specific rather than interchangeable, so what a farm animal or a fish makes is a comparison, never evidence about people. The panels below keep that distinction visible.

One gene is the fact; what follows from it is reasoning, so hold the two apart. Humans carry a single cathelicidin gene, and the peptide it yields turns up in antimicrobial, wound, and immune roles across this course. That one molecule covers several jobs is why its misfires show up in several places at once, which is the theme of the disease and safety units. No source behind this course tests what would happen if a pathogen resisted it, so read that as the shape of the problem rather than a measured finding.

Strip away the immunology and LL-37 is a small peptide of 37 amino acid residues, cut from the C-terminal end of a 170-residue precursor. Its sequence is on record, LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES in the FDA substance registry and in the last 37 residues of the UniProt precursor entry, so the two opening leucines the name refers to and the lysines and arginines the mechanism story rests on can be read off directly. What no source behind this course prints is a net charge figure for the peptide, so this course describes it as cationic and does not put a number on that. What the sources do pin down is which molecule is which, and the matrix below keeps the four apart.

Keeping those four apart is the single most useful habit for reading this literature. A paper that measures "cathelicidin" in a fluid may be measuring the precursor, the mature peptide, or a different peptide entirely, depending on which protease was present, and the assay usually does not say. When a later unit here reports a level, watch for which molecule was counted, because that question is open in several of the studies this course draws on.

Before the mechanisms, here is the honest picture sorted from best supported to missing. Laboratory antimicrobial and immune-signaling data are strong; animal wound and infection models are promising; controlled human clinical outcomes are thin; and long-term safety of LL-37 as a drug is essentially unstudied. Reading these tiers correctly, and refusing to let a lower tier borrow the confidence of a higher one, is the core skill of this course.

A handful of claims dominate online discussion of LL-37, from "natural antibiotic" to "heals any wound." Held against the evidence tiers, most are not flatly false so much as rounded up: a real but narrow finding inflated into a sweeping promise. Tap each claim below to see the honest verdict and where it sits on the evidence ladder.

Notice the pattern across the rows: the further a claim moves from a controlled dish and toward a whole living person, the thinner the evidence gets, and the more LL-37 double-edged nature matters. That is not cynicism, it is how honest reading of a complex peptide works.

Because humans rely on a single cathelicidin, LL-37 wears many hats at once. The hub below spreads its main roles so you can see the full scope before the deep-dive units. Each arm becomes its own unit later: direct microbe killing, immune recruitment, wound repair, antiviral defense, and endotoxin neutralization all trace back to the same short helix.

One peptide, five overlapping jobs, is efficient but risky. The same properties that let LL-37 do all of this also let it misfire, driving inflammation in psoriasis or aiding certain cancers. Keep this map in mind: every later unit is one arm of this hub examined in detail, benefits and hazards together.