ADRB1 is a G protein-coupled receptor that binds catecholamines (epinephrine and norepinephrine) with equal affinity to activate adenylate cyclase and the cAMP-dependent pathway 123. The receptor couples to Gs proteins and mediates Ras activation via RAPGEF2 2. Physiologically, ADRB1 regulates cardiac contractility and heart rate through sympathetic nervous system signaling 4, and influences sleep/wake cycles 56. Recently, ADRB1 has emerged as a critical immunoregulatory node. Exhausted CD8+ T cells upregulate ADRB1 expression; catecholamine engagement suppresses cytokine production and proliferation while promoting T cell exhaustion in chr10 infection and tumors 7. Mechanistically, epinephrine/norepinephrine-ADRB1 signaling activates PKA, which phosphorylates and inhibits antiviral response proteins MITA and VISA, suppressing innate immunity to DNA and RNA viruses—explaining increased infection susceptibility during stress 8. Clinically, ADRB1 genetic variants (Ser49Gly, Arg389Gly) significantly influence β-blocker efficacy in hypertension and arrhythmias 910. The Arg389Gly polymorphism associates with arrhythmia risk, particularly supraventricular tachycardia 10. β-blocker blockade of ADRB1 improves anti-tumor immunity when combined with checkpoint inhibitors in melanoma and pancreatic cancer 7, suggesting therapeutic potential beyond cardiovascular disease.