Secreted by the liver, hepcidin is a key iron hormone controls iron entry into circulation from absorptive enterocytes and iron-recycling macrophages by inducing FPN degradation. Iron loading and inflammation stimulate hepcidin transcription to prevent iron overload and sequester iron from pathogenic microorganisms (left panel). Iron deficiency and erythropoietic drive inhibit hepcidin transcription to provide adequate iron for erythropoiesis and other body requirements (right panel). Mediators of hepcidin regulation by iron, inflammation, and erythropoietic drive are indicated. Abbreviations: BMP, bone morphogenetic protein; HFE, hemochromatosis protein; TFR2, transferrin receptor 2; HJV, hemojuvelin; TMPRSS6 transmembrane protease serine 6; IL-6, interleukin 6; JAK, janus kinase; STAT3, signal transducer and activator of transcription 3; ERFE, erythroferrone.