ARRB1 (arrestin beta 1) is a multifunctional adapter protein that regulates G-protein coupled receptor (GPCR) signaling and serves diverse physiological roles beyond traditional receptor desensitization. ARRB1 mediates GPCR internalization through clathrin-coated pits and acts as a signaling scaffold for MAPK pathways, switching receptors from G-protein signaling to distinct arrestin-mediated signaling modes 1. The protein facilitates autophagy regulation, with ARRB1 interacting with autophagy core proteins like MAP1LC3/LC3 and promoting hepatocellular carcinogenesis through autophagy-mediated cell cycle progression 2. In metabolic regulation, ARRB1 inhibits non-alcoholic steatohepatitis progression by facilitating GDF15 maturation and transport to the Golgi apparatus 3. ARRB1 variants, particularly the Thr370Met polymorphism, significantly influence GLP-1 receptor agonist efficacy in diabetes treatment, with carriers showing enhanced glycemic response 1. In cardiovascular disease, AMPK phosphorylation of ARRB1 at Ser330 provides cardioprotection by attenuating β-adrenergic receptor-induced cardiac injury through enhanced PDE4 activity and reduced inflammasome activation 4. ARRB1 also modulates inflammatory responses, with reduced expression correlating with disease severity in liver fibrosis and serving as a therapeutic target through NF-κB pathway regulation 5. Pan-cancer analyses reveal ARRB1's prognostic significance and correlation with tumor immune microenvironments, particularly in kidney and lung cancers 6.