Hepcidin antimicrobial peptide (HAMP) (HAMP)

Hepcidin antimicrobial peptide, encoded by the HAMP gene, is a 25-amino acid peptide hormone that serves as the master regulator of systemic iron homeostasis in humans [1, 2]. It is primarily synthesized by hepatocytes in response to high iron stores or inflammatory signals, such as interleukin-6 [2, 4]. The hormone functions by binding to ferroportin, the only known cellular iron exporter, which triggers its internalization and lysosomal degradation [1, 3]. This action effectively traps iron within enterocytes and macrophages, thereby reducing intestinal iron absorption and the recycling of iron from senescent red blood cells [3]. Pathologically high levels of hepcidin contribute to the anemia of chronic disease by sequestering iron, while its deficiency leads to iron overload conditions like hereditary hemochromatosis [2, 4]. Therapeutic strategies targeting this pathway include hepcidin mimetics like rusfertide for iron overload and polycythemia vera, as well as hepcidin antagonists for treating inflammatory anemias [3]. Monitoring serum hepcidin and ferritin levels is essential for evaluating the efficacy and safety of these emerging treatments [4]. Sources: [1] UniProt (P81172); [2] Ganz T. World J Gastroenterol. 2013; [3] Camaschella C, et al. Blood. 2020; [4] NIH StatPearls: Physiology, Hepcidin.

Other names

HepcidinLEAP-1Liver-expressed antimicrobial peptide 1Hepcidin-25HEPCHAMP

Hepcidin regulates systemic iron levels by binding to the cellular iron exporter ferroportin (SLC40A1), which induces its phosphorylation, internalization, and subsequent lysosomal degradation [1, 3]. This process prevents the efflux of iron from duodenal enterocytes, macrophages, and hepatocytes into the blood plasma, thereby lowering systemic iron availability [2, 4].