ADRB3 is a G protein-coupled receptor for catecholamines that regulates energy homeostasis primarily through adipose tissue function. The receptor couples to both Gs and Gi proteins, activating adenylate cyclase and cAMP-PKA signaling, or alternatively triggering ERK1/2 MAP kinase cascades 12. Norepinephrine is the preferred physiological agonist over epinephrine 1. ADRB3 drives lipolysis and thermogenesis in brown and white adipose tissue, and mediates vascular relaxation and negative cardiac inotropic effects 13. Disease relevance is substantial. ADRB3 downregulation in obesity occurs through a TRIB1-mediated pathway, contributing to catecholamine resistance and impaired lipolysis 4. However, human brown adipose thermogenesis surprisingly operates primarily through β2-AR rather than β3-AR, limiting clinical efficacy of β3-AR agonists in humans 5. ADRB3 amplification correlates with chemotherapy resistance in breast cancer 6. Conversely, β3-AR activation via mirabegron promotes lymphangiogenesis in perivascular adipose tissue, preventing aortic dissection/aneurysm 7. The Trp64Arg polymorphism associates with altered adipokine levels and dyslipidemia, particularly in obese Asian women, though it shows no direct coronary heart disease association 89. ADRB3 represents both a metabolic regulator and emerging therapeutic target for cardiovascular and metabolic diseases.