ARRDC1 (arrestin domain containing 1) functions as a ubiquitin ligase adapter that recruits E3 ligases to substrate proteins, facilitating their ubiquitination-dependent degradation 1. A primary role involves regulating extracellular vesicle (EV) biogenesis, particularly ARRDC1-mediated microvesicles (ARMMs) that bud from the plasma membrane 2. ARRDC1 mediates protein transport between cells through EV release, including incorporation of cargo like PKM2 into ectosomes in hepatocellular carcinoma 3. Mechanistically, ARRDC1 negatively regulates NOTCH signaling by promoting ITCH-mediated NOTCH1 ubiquitination and degradation 1. Clinically, ARRDC1 demonstrates antiviral activity by mediating ubiquitination and degradation of Semliki Forest virus nsP4, inhibiting viral replication 4. ARMMs provide neuroprotection against cadmium-induced toxicity by enriching antioxidative stress proteins 5. Therapeutically, engineered ARMMs serve as versatile delivery platforms for CRISPR-Cas9 and mRNA therapeutics with cell-type specificity 67, and fusing ARRDC1 with p53 enhances EV loading for tumor suppression 8. ARRDC1 dysregulation occurs in diffuse large B-cell lymphoma where the antisense transcript ARRDC1-AS1 promotes autophagy and cancer progression 9.