We also have shown that sortilin-knockout mice develop prion disease with shorter incubation times and rapid brain accumulation of PrPSc after inoculation with prions, compared to control wild-type (WT) mice [31], suggesting that the sortilin-mediated trafficking of PrPC and PrPSc to lysosomes could be a host defense mechanism in prion diseases. Here, PRNP is linked to prion disease.