It has been shown that the non-structural, flexible N-terminal domain, which includes various specific regions such as the polybasic region, OR regions, and post-OR region, has a role in not only the normal function of PrPC but also in the pathogenesis of prion diseases through regulation of the conversion of PrPC to PrPSc and the neurotoxicity of PrPSc. This evidence concerns the gene PRNP and prion disease.