ER stress was proposed to play a key role in prion diseases since stress-regulated ER chaperons, such as Grp78/BiP and Grp58/Erp57, were induced in sporadic and variant CJD, and in bovine spongiform encephalopathy, and their up-regulation correlated with disease progression in prion-infected mice [38], [43], [44], [45], [46]. This evidence concerns the gene PDIA3 and prion disease.