UVRAG (UV radiation resistance associated) is a multifunctional regulator of cellular homeostasis with dual roles in autophagy and DNA repair. Primary function: UVRAG functions as a critical component of the Class III phosphatidylinositol 3-kinase (PtdIns3K) complex, regulating autophagosome maturation through interactions with BECN1, PIK3C3, and RUBCN 1. Mechanism: UVRAG ubiquitination by SMURF1 at lysine residues 517 and 559 promotes autophagosome maturation by decreasing UVRAG-RUBCN association, while CSNK1A1-mediated phosphorylation at Ser522 inhibits this process 1. The protein is also involved in DNA double-strand break repair through association with the DNA-dependent protein kinase complex, promoting non-homologous end joining (NHEJ) 2. Additionally, UVRAG maintains centrosome stability and ensures proper chromosome 11. Disease relevance: UVRAG dysfunction impairs autophagy flux, with evidence linking its dysregulation to hepatocellular carcinoma (HCC) growth; elevated UVRAG phosphorylation at Ser522 correlates with poor HCC prognosis 1. The protein participates in quality control mechanisms relevant to neurodegenerative diseases through autophagy-lysosomal degradation pathways 3. Clinical significance: Targeting UVRAG ubiquitination or preventing Ser522 phosphorylation enhances lysosomal EGFR degradation and inhibits HCC growth, offering therapeutic potential 1. Small-molecule kinase inhibitors targeting autophagy-related kinases that regulate UVRAG represent emerging cancer treatment strategies 4.