Ferroportin-1 (FPN (also SLC40A1))

Ferroportin-1 (FPN or SLC40A1) is the only known iron exporter in mammals, encoded by the SLC40A1 gene[1][2][3][5][7][8]. It is a transmembrane protein primarily responsible for transporting iron from enterocytes, hepatocytes, and reticuloendothelial macrophages into the bloodstream, thus regulating systemic iron balance. FPN function is tightly regulated by the hormone hepcidin: when plasma iron is high, hepcidin binds FPN, triggering its degradation and thereby reducing iron export; when iron is low, decreased hepcidin leads to increased FPN at cell surfaces and thus greater iron release. Mutations in SLC40A1 cause hereditary hemochromatosis type 4 (ferroportin disease), characterized by pathological iron overload and end-organ damage[3][4]. Ferroportin also plays a role in preventing iron-mediated oxidative damage and in controlling ferroptosis, a form of cell death linked to various diseases including cancer[2]. FPN is part of the major facilitator superfamily and is expressed in tissues inherently involved in iron absorption and storage, such as intestinal enterocytes, macrophages, hepatocytes, and placental syncytiotrophoblasts[1][8].

Other names

Solute carrier family 40 member 1SLC40A1FPN1IREG1SLC11A3MSTP079MTP1HFE4Iron-regulated transporter 1FerroportinIron-regulated gene 1SLC40 iron transporter

Hepcidin binds to ferroportin, causing its internalization and degradation, thus reducing iron efflux. Modulation of the hepcidin–ferroportin interaction to restore or inhibit iron export.