Circulating hepcidin concentration is regulated by molecular mediators that communicate the status of iron stores (Tf, TfR, TfR2, HFE, HJV, BMP-6, Smad4), inflammation (IL-6), and erythroid drive (GDF15, TWSG, and likely others). Hepcidin promotes the internalization and degradation of Fpn on tissue macrophages. Erythrophagocytosis and inflammation also transcriptionally and translationally regulate Fpn within the macrophage.