Chronic ERS activation via the IRE1α‐XBP1, ATF6, and PERK pathways drives vascular endothelial dysfunction (reduced NO bioavailability, increased ET‐1), renin‐angiotensin system (RAS) hyperactivation, sympathetic overactivation, and vascular smooth muscle cell (VSMC) maladaptive proliferation/apoptosis, collectively promoting hypertension progression and end‐organ damage. The gene discussed is REN; the disease is Hypertension.