Central role of hepcidin in organismal iron homeostasis. Cell-associated, GPI-linked hemojuvelin (HJV) is proposed to act as a coreceptor for bone morphogenetic protein (BMP) ligands and BMP receptors (BMP-Rs). Interaction of HJV with BMP ligands and 2 BMP-Rs on the cell surface generates an active signaling complex. This complex subsequently activates the intracellular SMAD signaling pathway to induce hepcidin expression. Hepcidin, a peptide secreted by the liver, promotes internalization and degradation of the iron exporter ferroportin (FPN). The pathway by which HFE and transferrin receptor 2 (TfR2) control the expression of hepcidin is unclear. Importantly, mutations in HJV, HFE, or TfR2 lead to inappropriately low levels of hepcidin. Dcytb indicates duodenal cytochrome b; DMT1, divalent metal transporter 1. This figure is a modified version of that published in Dunn et al,²  copyright Elsevier; adapted with permission by Alice Y. Chen.