Similar to our findings, GRP78 has been found to interact with the misfolded form of the prion protein and inhibit its accumulation and propagation, and play a key role in the defense against prion diseases.46 In addition to direct regulation of proper tau protein folding, GRP78 may inhibit tau phosphorylation and aggregation by preventing PERK activation. This evidence concerns the gene HSPA5 and prion disease.