PKCα is a novel regulator of Fpn in diabetes. Diabetic hyperactivation of PKCα upregulates intestinal Fpn expression in a hepcidin-independent manner. PKCα decreases endocytic trafficking of Fpn and suppresses hepcidin-induced ubiquitination, and degradation of Fpn. Inhibition or genetic disruption PKCα alleviates iron overload. Fpn, ferroportin; PKCα, protein kinase C alpha.