ARRB2 (β-arrestin 2) is a multifunctional adapter protein that primarily regulates G-protein coupled receptor (GPCR) signaling through desensitization, internalization, and activation of alternative signaling pathways. ARRB2 mediates receptor internalization by acting as an endocytic adapter that recruits GPCRs to clathrin-coated pits, with different receptors showing distinct internalization patterns 1. Beyond classical GPCR regulation, ARRB2 functions as a signaling scaffold for multiple pathways including MAPK/ERK, AKT, and inflammasome signaling 2 3. In pancreatic β-cells, ARRB2 differentially regulates GLP-1 and GIP receptor signaling, dampening insulin secretion through GLP-1R while being required for GIP-induced insulin potentiation 4. ARRB2 also exhibits anti-inflammatory properties by directly associating with NLRP3 inflammasome components, inhibiting pro-inflammatory cytokine release 3 5. Disease relevance includes pulmonary arterial hypertension, where ARRB2 upregulation following BMPR2 loss contributes to abnormal smooth muscle cell proliferation and contractility 6. In cancer, ARRB2 promotes progression through MAPK pathway activation in prostate cancer 2 and endometrial carcinoma 7. ARRB2's diverse roles in metabolic regulation, inflammation, and disease pathogenesis highlight its potential as a therapeutic target across multiple conditions.