The conversion is induced by prion infections (for example, variant Creutzfeldt-Jakob disease (vCJD), iatrogenic CJD, Kuru), mutations (familial CJD, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia (FFI)) or unknown factors (sporadic CJD (sCJD)), and it is considered to occur after PrPC has reached the plasma membrane or has been re-internalized for degradation [30]. Here, PRNP is linked to fatal familial insomnia.