The cardinal roles of ferroportin and its partners in controlling cellular iron in and out

In mammals, ferroportin (FPN) is the only known iron exporter, and it functions as a “water tap” in controlling iron absorption from the diet, iron egress from macrophages and other cells. However, its function is implemented not by itself but by a complex with many partners involved. In the current study, we elaborate on the direct partners in calibrating the capability of FPN in exporting iron out of cells, such as ceruloplasmin (CP), hephaestin (HP) and poly(rC)-binding protein 2 (PCBP2). We also recapitulate the current understandings of the regulation of FPN concentration at the post-transcriptional level. Considering the importance of FPN in finetuning iron homeostasis, a few therapeutic options are pursued to target FPN and its partners in treating iron diseases. Nonetheless, limited knowledge has been obtained on direct and indirect partners of FPN, so that more efforts should be invested including their therapeutic values.