APP and Alzheimer disease: Two main UPR proteins, including PERK (encoded by EIF2AK3) and IRE-1 (encoded by ERN1), were upregulated and activated in AD due to misfolded Aβ oligomers (Joshi et al., 2016), although a recent critical review suggested that the involvement of ER stress in AD might be exaggerated by the misuse of APP/PS1-overexpressing AD mouse models (Hashimoto and Saido, 2018).