A model of hepcidin regulation by iron Tf (a) and intracellular iron (b). a Increased iron Tf concentrations stabilize TfR2 protein, HFE is displaced from TfR1 and associates with TfR2. The HFE-TfR2 complex likely interacts with the HJV-BMP receptor (BMPR), BMP signaling is potentiated and hepcidin transcription increases. b Elevated intracellular iron increases BMP6 production. Secreted BMP6 binds to the HJV-BMPR complex, stimulates Smad signaling, and increases hepcidin transcription.