Figure 2. PrP^C-mediated iron homeostasis.

PrP^C facilitates uptake of Tf-Fe³⁺ and non-Tf-bound iron (Fe³⁺) by its ferrireductase activity. Tf iron released in the endosome is reduced to Fe²⁺ for transport through DMT1. Non-Tf bound iron is reduced at the plasma membrane for transport through ZIP14 and other divalent metal transporters. Loss of PrP^C function reduces iron uptake, and creates iron deficiency Singh 2014).