A. Early stages of terminal differentiation (Proerythroblast) are characterized by PCBP1-mediated, iron accumulation in ferritin. NCOA4 levels are low and ferritin turnover is slow. B. Mid stages of development (basophilic to orthochromatic erythroblast) are characterized by high levels of iron flux through ferritin, high rates of ferritin turnover, and high rates of iron transfer to the mitochondria. A direct mechanism involving Mucolipin1 (Mln1) and Mitofusin 2 (Mfn2) may be operating. C. Late stage development (Reticulocyte) is characterized by low levels of iron uptake and heme synthesis. Ferritin levels are low and intracellular organelles are rapidly lost. Iron may be directly transferred to mitochondria. Modified from [22]. Ryu MS, Zhang D, Protchenko O, Shakoury-Elizeh M, Philpott CC: PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis. J Clin Invest 2017, 127:1786-1797.