The subsequent observation that pharmacological inhibition of PDIs causes an increase in proteinase K-resistant PrPSc levels in a subset of ScN2a cell clones is exciting as it suggests PDIs may, under certain circumstances, be protective in the context of prion disease, thereby extending observations from an earlier report which documented an increase in Pdia3 levels in prion infected mice and an inverse correlation of PrPSc toxicity and Pdia3 expression levels in mouse neuroblastoma cells [40]. Here, PDIA3 is linked to prion disease.