Scheme of the function of erythrocytic FPN in systemic iron homeostasis. FPN on reticuloendothelial macrophages exports iron recycled from senescent RBCs into the blood and contributes the majority of the daily iron influx. FPN on intestinal epithelial cells transports iron absorbed from diets into the blood to compensate for the iron loss via skin and epithelium shredding, which is estimated to account for ∼10% daily iron consumption. FPN on hepatocytes also exports iron into the blood when blood iron levels are lower, from the iron deposits that are stored under iron-replete conditions. Here we found that FPN on erythroblasts and RBCs also contributed a significant amount of iron into the blood. Considering that the levels of FPN on erythroblasts are as abundant as on macrophages, the contribution of iron from erythroid cells could exceed that from intestine or hepatocytes under homeostatic conditions. Thus, FPN on erythroblasts plays an essential role in maintaining systemic iron homeostasis, especially under iron deficiency conditions, and FPN on RBCs protects RBCs against oxidative stress and malaria infection.