The unstructuredN-terminal region (NTR) of PrP is not incorporatedinto the proteinase-K resistant amyloid core of the prion fibril andnot necessary for prion replication.4,48 Conversely,octarepeat expansions in the NTR of PrP cause genetic prion disease,49 and the presence of the NTR facilitates theformation of β-sheet rich oligomeric assemblies,50 suggesting a mechanistic role of the NTR inprion assembly. This evidence concerns the gene PRNP and prion disease.