PRNP and prion disease: However, the recent characterization of variably protease-sensitive prionopathy, a novel phenotype of sporadic prion disease associated with distinctive PrPSc properties and clinico-pathological features, has clearly shown that the formation of C-terminally truncated, unglycosylated and anchorless fragments, thought to be GSS-specific until recently, may also occur in sporadic prion disease in the absence of any mutation [102], a finding which supports the view that most PrPSc conformational diversity may develop independent of the presence of PRNP mutations.