The BMP/SMAD signaling pathway requires upstream auxiliary factors: (a) Hemojuvelin (HJV), a BMP co-receptor; (b) The hemochromatosis protein HFE, an atypical major histocompatibility complex class 1 (MHC class 1) type molecule; and (c) Transferrin receptor 2 (TfR2), a sensor of iron-loaded plasma transferrin. The gene discussed is HFE; the disease is hemochromatosis.