 Iron regulatory proteins, IRPs, regulate iron metabolism by binding to RNA stem loop structures known as iron-responsive elements, IREs, and target mRNAs. RP1 and RP2 are two members of the mammalian RP protein family, and they have redundant functions. IRP1-forward slash and IRP2-forward slash mice are viable, but IRP2-forward slash mice display neurodegenerative symptoms and microcytic hypochromic anemia. Recent studies indicate that RP1 plays an essential function in orchestrating the balance between erythropoiesis and bodily iron homeostasis, and it has a critical role in the pulmonary and cardiovascular systems. This review summarizes recent progress made in understanding the physiological roles of IRP1 and IRP2 and discusses their implications for clinical research on patients with idiopathic polycythemia, pulmonary hypertension, and neurodegeneration. This article was authored by Do Young Yi Zhang, Monic C. Gosh, and Tracy A. Ruo. We are article.tv. Links in the description below.