Iron is an essential co-factor for several metabolic processes, including the generation of adenosine triphosphate (ATP) in mitochondria, which is required for axonal function and regeneration. However, it is not known how mitochondria in long axons, such as those in sciatic nerves, acquire iron in vivo . Due to their close proximity to axons, Schwann cells (SCs) are a likely source of iron for axonal mitochondria in the peripheral nervous system. Here we demonstrate the critical role of iron in promoting neurite growth in vitro using iron chelation. We also show that SCs express the molecular machinery to release iron, namely, the iron exporter, ferroportin (Fpn) and the ferroxidase ceruloplasmin (Cp). In Cp knockout (KO) mice, SCs accumulate iron, because Fpn requires to partner with Cp to export iron. Axons and SCs also express the iron importer transferrin receptor 1 (TfR1), indicating their ability for iron uptake. In teased nerve fibers, Fpn and TfR1 are predominantly localized at the nodes of Ranvie...