PRNP and prion disease: Therefore, the most stringent approach to prove the prion hypothesis needs to fold exogenously produced recombinant PrP (recPrP) to the PrPSc conformation in a test tube and demonstrate that the in vitro-generated recPrPSc can seed the PrPC-to-PrPSc conversion and cause bona fide TSEs (also known as prion disease) in a suitable host (Figure 1).