Regulation of hepcidin. Schema illustrating some of the complex regulation of hepcidin by iron status, hypoxia, and erythropoietic demand. Increased iron status induces hepcidin through: bone morphogenetic protein 6 (BMP6), bone morphogenetic protein receptors (BMP-Rs), hemojuvelin (HJV), hemochromatosis protein (HFE), and transferrin receptor 1 (TfR1) and TfR2. Hypoxia and increased erythropoiesis work through: erythropoietin (EPO), erythropoietin receptor (EPOR), and the erythropoietic regulators, erythroferrone (ERFE), growth differentiation factor 15 (GDF15), and twisted gastrulation BMP signaling modulator 1 (TWSG1), to inhibit hepcidin expression. Iron absorbed by duodenal enterocytes and recycled from Hb from senescent red blood cells (RBCs) by macrophages is transported into the circulation by ferroportin 1 (Fpn1). Hepcidin secreted by the hepatocyte binds to Fpn1, causing its internalization and degradation, thereby limiting iron transport. Hb, hemoglobin.