In sporadic and inheritedprion diseases, for example, sporadic Creutzfeldt–Jakob disease(CJD) and fatal familial insomnia (FFI), respectively, the causativePrPSc are generated by the spontaneous conformational conversionof the endogenous normal isoform PrP (PrPC) into PrPSc, with or without the aid of pathogenic mutations in the PRNP gene. The gene discussed is PRNP; the disease is fatal familial insomnia.