HAMPs

HAMPs, or hepcidin antimicrobial peptides, are a family of small, cysteine-rich peptides that play a central role in iron regulation and, in some contexts, antimicrobial defense. In humans, the HAMP gene encodes hepcidin, a peptide mainly produced by the liver and released into the bloodstream. The mature form most often present in humans is hepcidin-25, though other length variants exist in different species. Hepcidin is stabilized by disulfide bonds and is generated by processing a larger precursor.

The primary physiological function of HAMPs is to control systemic iron homeostasis. Hepcidin binds to ferroportin, the only known iron exporter present on enterocytes, macrophages, and hepatocytes. This interaction triggers ferroportin internalization and degradation, reducing iron export into plasma and lowering serum iron levels. While hepcidin also possesses antimicrobial activity in vitro, its principal in vivo role is the regulation of iron availability, which indirectly influences microbial growth and erythropoiesis.

Expression and regulation are complex. Hepcidin production is upregulated by iron loading and inflammatory signals, especially interleukin-6, which activates the JAK-STAT pathway. The BMP/SMAD signaling axis also contributes to iron-dependent transcription. Conversely, iron deficiency, hypoxia, and increased erythropoietic activity suppress hepcidin expression. Interacting proteins such as hemojuvelin, transferrin receptor 2, and HFE modulate the regulatory network.

Clinical significance is linked to hepcidin imbalance. Deficiency or impaired regulation of HAMP leads to iron overload disorders, whereas excess hepcidin can cause iron-restricted erythropoiesis and anemia of inflammation. Therapeutic strategies aim to modulate hepcidin levels or activity to treat iron disorders. HAMPs are conserved across vertebrates with species-specific isoforms and regulatory details.