(i) Heme-bound iron is absorbed into duodenal enterocytes, possibly via HCP1. Enterocyte HO-1 releases iron from heme’s porphyrin ring, producing Fe²⁺, biliverdin, and carbon monoxide. Fe²⁺ iron is then exported into the circulation by FPN1. (ii) Absorbed Fe³⁺ is reduced to Fe²⁺ at the brush border by low pH and ferrireductases, enabling its transport by DMT1 into duodenal enterocytes. Fe²⁺ is either bound to FTN within the enterocyte, limiting the intracellular pool of free iron, or released into the circulation by FPN1, where it is oxidized to Fe³⁺ by hephaestin (HPE) and ceruloplasmin (CP) and bound to TF for transport. (iii) Macrophages identify senescent RBCs no longer expressing CD47 via SIRPα and recycle RBC iron through phagocytosis. Upon fusion of phagosomes with lysosomes, heme is released from hemoglobin and transported to the cytosol via HRG1. In the cytosol, heme-bound iron is extracted by HO-1 and exported by FPN1. Fe²⁺ is then oxidized to Fe³⁺ by CP and binds to TF for transport. (iv) When systemic iron levels are sufficiently replete, hepcidin is produced by the liver, binds to FPN1 on macrophages and enterocytes, and promotes its degradation. This prevents intestinal and macrophage iron release into the circulation. Binding of BMP6 to BMP receptor and its coreceptor HJV activates SMAD signaling and promotes transcription of hepcidin.