Hepcidin–ferroportin axis (HAMP-FPN)

The Hepcidin–ferroportin axis is the primary regulatory pathway governing systemic iron homeostasis in vertebrates (Ganz T, 2013). Hepcidin, a peptide hormone produced by the liver, serves as the ligand that binds to ferroportin, the only known cellular iron exporter (Nemeth E & Ganz T, 2021). Upon binding, hepcidin induces the internalization and degradation of ferroportin, thereby sequestering iron within cells and reducing its concentration in the blood plasma (Xiao J, et al., 2020). This interaction is critical for managing iron levels in response to dietary intake, erythropoietic demand, and inflammatory signals. Pathological disruption of this axis leads to significant clinical conditions: high hepcidin levels cause anemia of inflammation by trapping iron in macrophages, while low hepcidin levels lead to iron overload in hereditary hemochromatosis (Ganz T, 2013). Therapeutic interventions target this axis using hepcidin mimetics like rusfertide to treat iron overload and polycythemia vera, or hepcidin antagonists like lexaptepid pegol to mobilize iron for erythropoiesis in chronic diseases (Kremyanskaya M, et al., 2024; Xiao J, et al., 2020). Additionally, oral ferroportin inhibitors such as vamifeport are being developed to mimic the effects of hepcidin for conditions like beta-thalassemia (Manolova V, et al., 2019).

Other names

Hepcidin-Ferroportin interactionHAMP-SLC40A1 interactionHepcidin-Ferroportin pathway

Hepcidin mimetics and ferroportin inhibitors reduce iron export into plasma by inducing degradation or blocking the transporter, while hepcidin antagonists prevent ligand-induced degradation to increase iron availability.