Hepcidin-25 (HAMP)

Hepcidin-25 is a 25-amino acid peptide hormone produced primarily by hepatocytes that serves as the master regulator of systemic iron homeostasis (UniProt P81172). It exerts its biological effect by binding to ferroportin, the only known mammalian cellular iron exporter, triggering its internalization and degradation (PubMed: 23024003). This action effectively traps iron within macrophages and enterocytes, thereby reducing the concentration of iron in the plasma. Dysregulation of hepcidin is a hallmark of several iron-related disorders; excessive levels lead to iron-restricted anemias such as anemia of chronic disease, while insufficient levels result in iron overload conditions like hereditary hemochromatosis (PubMed: 31015130). Therapeutic strategies targeting the hepcidin-ferroportin axis include hepcidin mimetics (e.g., Rusfertide) to treat iron-loading anemias and hepcidin antagonists (e.g., Lexaptepid pegol) to mobilize iron for erythropoiesis in inflammatory states (PubMed: 33536248). Monitoring serum hepcidin levels is increasingly used as a diagnostic tool to differentiate between various types of anemia and to guide personalized iron therapy.

Other names

Liver-expressed antimicrobial peptide 1LEAP-1Hepcidin antimicrobial peptideHEPC

Hepcidin binds to the cellular iron exporter ferroportin, inducing its internalization and lysosomal degradation, which prevents iron release from macrophages and dietary iron absorption in the gut.