EIF2AK3 and cognitive disorder: During the early stage of the ERS, adaptive activation of PERK is a protective cellular mechanism [45]; however, persistent activation of PERK causes hyperphosphorylation of eIF2α at Ser51 [49], which can inhibit general translation initiation, lead to a reduction of critical memory proteins [17,50], further resulting in cognitive disorder and neurodegeneration [26,45,51].