Although the capacity to avoid retrotranslocation in the cytosol and ubiquitination is not invariantly associated with PrP mutations, there is evidence that the expression of mutant prion proteins associated with familiar CJD (e.g., V210I and M323R) induces downregulation of the ER chaperone Bip and the activity of Hrd1 ubiquitin ligase (Peters et al., 2016). Here, PRNP is linked to Creutzfeldt Jacob disease.