The neurodegeneration and anemia of Irp2-/- mice and the polycythemia and pulmonary hypertension of Irp1-/- mice underline the essential role of IRP/IRE machinery in regulating cellular and systemic iron homeostasis, and also suggest that mutations of IRP1 and IRP2 could underlie some human diseases. This evidence concerns the gene IREB2 and anemia.