The ERS-specific inhibitor 4-PBA inhibited the Ang-II-induced p-PERK-p-eIF2-α-ATF4-CHOP-Caspase 12-axis expression in HL-1 cells and rat left atrial tissue, improving atrial fibrosis, AF susceptibility and deterioration of left atrial function and reducing HL-1 cell apoptosis. Here, EIF2AK3 is linked to atrial fibrillation.