Although a defined stoichiometry of PrPSc glycoforms and of PrPC glycoforms is dispensable for efficient conversion by protein misfolding cyclic amplification40 and glycosylation is not necessary for the acquisition of protease resistance by PrP in scrapie-infected cells41, glycosylation determines prion replication, strains, cytotoxicity and neuroinvasion42–44. Here, PRNP is linked to scrapie.