A summarized scheme of the UPR regulation on human cardiac ion channels. Activated UPR downregulates selective ion channels, leads to prolonged APD and reduced dV/dtmax, which can contribute to electrical remodeling and arrhythmias. The PERK branch downregulates Nav1.5, Kv4.3, hERG, and KvLQT1, while the IRE1 branch downregulates Nav1.5, Cav1.2, hERG, and KvLQT1.