When UPR is induced, Bip is attracted to bind to the unfolded proteins accumulated in the ER to keep the correct protein folding and is thereby released from PERK, IRE‐1 and ATF‐6, which are consequently phosphorylated and activated.14, 15, 16 Although the initial UPR protects the cell from the toxicity of misfolded proteins in the ER, prolonged UPR activation may participate in the pathogenesis of protein misfolding diseases, such as AD.17, 18, 19, 20. This evidence concerns the gene ERN1 and Alzheimer disease.