PRNP and human prion disease: The cellular prion protein (PrPC) was first described as the substrate for PrP scrapie (PrPSc) (Prusiner, 1982; Brandner et al., 1996a,b), a misfolded and aggregation-prone form of the protein detected in brain tissue of animals diagnosed with transmissible spongiform encephalopathies, now often called prion diseases.