The protein only hypothesis proposes that prion disease is associated with the misfolding of the normal cellular prion protein (PrPC) into a more protease-resistant, β-sheet rich conformation (PrPSc) [1], which can be induced by infection with exogenous PrPSc, spontaneous accumulation of PrPSc, or genetic mutations in the prion gene (PRNP) [2]. This evidence concerns the gene PRNP and prion disease.