ARRDC3 (arrestin domain containing 3) is an α-arrestin adapter protein that regulates cell-surface receptor expression and protein degradation through ubiquitin-proteasome pathways 1. Primarily, ARRDC3 controls GPCR trafficking by facilitating NEDD4-mediated ubiquitination and endocytic degradation of activated β2-adrenergic receptors (ADRB2) 12, and likely regulates other GPCRs similarly 3. Beyond adrenergic signaling, ARRDC3 modulates Hippo pathway activity by promoting YAP lysosomal degradation, thereby suppressing viral replication 4. Clinically, ARRDC3 dysfunction associates with multiple diseases. In alcoholic liver disease, elevated ARRDC3 promotes hepatic steatosis by inhibiting stearoyl-CoA desaturase-1 ubiquitin-dependent degradation 5. ARRDC3 upregulation impairs trophoblast invasion and tube formation in preeclampsia 6, while reduced expression correlates with aggressive prostate cancer phenotypes and poor biochemical recurrence-free survival 7. Conversely, ARRDC3 genetic variants associate with increased glioma susceptibility 8. In gastric cancer, ARRDC3 acts as a tumor suppressor by mediating ITGB4 degradation and inhibiting PI3K/AKT signaling 9. HPV cervical cancer association studies implicate ARRDC3 in viral entry mechanisms 10. These findings establish ARRDC3 as a multifunctional regulatory protein with context-dependent therapeutic potential across diverse pathologies.