PRNP and prion disease: Among the many functionsattributed to PrPC, i.e., cell signaling, antioxidation,and myelination,17 phylogenetic analysisindicates that PrPC is evolutionarily linked to the Zrt-and Irt-like protein (ZIP) family of divalent metal ion transporters.24 This suggests that one biological role for PrPC might be to regulate metal ion homeostasis—metal imbalancehas been suggested to be part of the pathology of prion diseases.25−27