What Is Hepcidin? A 25-Residue Disulfide-Rich Hormone

By What Peptides Editorial Team · Updated 2026-09-14 · Part of Peptide Structure, Classification & Scientific Terminology

Hepcidin is a 25-residue peptide hormone produced mainly by liver hepatocytes, and it is the reference example of a disulfide-rich peptide. The mature form carries four intramolecular disulfide bonds, formed by eight cysteine residues out of twenty-five, and those bridges clamp a short hairpin into an unusually rigid fold. It is translated as an 84-residue preprohormone and processed down to the active form, and shorter N-terminally truncated versions also occur in blood and in urine. Its described role in mammalian physiology is as the systemic regulator of iron flux, acting on the cellular iron exporter ferroportin. Everything on this page is descriptive biochemistry written for education. It is not guidance of any kind, and no part of it should be read as advice about any person.

The name is worth one sentence. Hepcidin was identified independently by two groups and therefore carries two names: hepcidin, from hepatic and the bactericidal activity first observed for it, and LEAP-1, for liver-expressed antimicrobial peptide. The gene is HAMP. The antimicrobial naming reflects a fold and a cysteine pattern shared with defensin-type peptides, while the hormone naming reflects the function that later turned out to matter. Both names describe the same molecule, which is a useful reminder that a peptide name often records the experiment that found it rather than the biology that follows. Our peptide structure and classification reference sets out how disulfide-rich peptides are grouped; this page stays with hepcidin's own parameters.

Structure: length, disulfides and precursor processing

The HAMP gene encodes an 84-residue preprohormone. An N-terminal signal peptide targets the chain for secretion and is removed, leaving a proregion that is cleaved by proprotein convertases of the furin family to release the C-terminal 25-residue peptide. The mature hormone is about 2.8 kDa, with a reported monoisotopic mass near 2789 Da for the fully oxidised form. Shorter forms of 20 and 22 residues are produced by further trimming at the N-terminus and are found in urine as well as in plasma. Reported structural work describes a distorted beta-hairpin with a flexible N-terminal segment.

The N-terminal segment is not decorative. Studies of truncated forms report that the first few residues are required for the interaction with ferroportin, so hepcidin-20 shows little or no activity in ferroportin internalisation assays even though the disulfide core is intact. The disulfide connectivity is also unusual, since reported connectivities include a vicinal bridge between adjacent cysteines. The chemical consequence of eight cysteines in twenty-five residues is a peptide that resists heat and proteolysis far better than a linear chain of the same length, which is why disulfide-rich peptides are treated as a structural class rather than as an oddity.

What hepcidin does, described neutrally

The described mechanism is short and it is worth stating without embellishment. Ferroportin is the only known cellular iron exporter in mammals, and it sits on the surface of duodenal enterocytes, on macrophages that recycle iron from senescent red cells, and on hepatocytes that store iron. Hepcidin binds to ferroportin, and that binding is reported to trigger phosphorylation of the exporter, followed by ubiquitination, internalisation and lysosomal degradation. With fewer exporter molecules on the cell surface, less iron leaves the cell and less reaches the plasma. The consequence is that dietary iron absorption and macrophage iron recycling both fall, and iron that would have been exported is retained and later lost when intestinal cells are shed.

The inputs that set the level of hepcidin are the other half of the picture, and they are described in the literature as three broad signals. Iron loading raises hepcidin transcription through a bone morphogenetic protein and SMAD-dependent pathway whose upstream sensors include hemojuvelin and the transferrin receptors. Inflammation raises it through interleukin-6 and STAT3 signalling. Erythropoietic drive suppresses it, with erythroferrone described as one mediator. Hypoxia and iron deficiency act through the same set of routes in the opposite direction. All of this is physiology reported in the literature, and none of it changes the standing of this page, which is descriptive and educational rather than advisory.

Measurement is worth a note because it is a genuine analytical problem. Hepcidin is small, heavily cross-linked and present at low concentration, so immunoassays from different groups have not always agreed on absolute values, while mass-spectrometric methods need enrichment and careful calibration. A reader comparing two published figures should check which form was measured and which method produced the number.

Why the fold matters, and the limits of this page

From a chemistry point of view, the interesting number is 105. Eight cysteines can be paired into four disulfide bonds in 105 distinct ways, and only one of those pairings is the native fold, so the oxidative folding of a peptide like this is a real synthetic problem rather than a formality. Rigidity is the reward: once the correct bridges are in place, the peptide holds a defined surface, resists proteases and survives conditions that would disorder a linear chain. That is the general argument for studying disulfide-rich peptides as a class, and hepcidin is the compact example that makes the argument concrete.

To be explicit about limits: this page states no dose, no schedule, no route, and no protocol for any person or animal. Hepcidin is not a supplement, not a cosmetic ingredient, and not a consumer product, and it appears in no product category this site reviews. Its interest is as a physiological regulator, as a research analyte and as a target described in the clinical literature. Anyone with a health question needs a licensed clinician, and anyone with a research question needs the primary literature and an assay matched to the question. What this page offers is the stable part: length, disulfide count, mass, precursor length, gene name and binding partner, all of which are properties of the molecule rather than of any interpretation placed upon it.

For readers who arrived here through the naming problem, the other names one peptide can carry explains how a single molecule ends up with two names, and what research use only does and does not mean explains the status of material a laboratory would use to study it.

This page is part of the Peptide Structure, Classification & Scientific Terminology guide.