DDB2 (damage-specific DNA binding protein 2) is a DNA damage recognition factor that facilitates global genomic nucleotide excision repair (GG-NER), particularly in response to UV-induced DNA lesions 1. As a component of the DDB complex, DDB2 localizes to damaged DNA sites and functions within Cul4-RING E3 ubiquitin ligase complexes to promote repair through ubiquitin-mediated proteolysis 2. Mechanistically, DDB2 coordinates nucleotide excision repair in chr11 through multiple cellular regulatory levels, including nuclear translocation and transcriptional induction 2. Mutations in DDB2 cause xeroderma pigmentosum complementation group E (XP-E), characterized by extreme UV sensitivity and skin cancer predisposition 2. DDB2 functions as a tumor suppressor by controlling p53-mediated apoptosis after UV exposure; DDB2-deficient mice exhibit enhanced UV-induced skin carcinogenesis and resistance to UV-induced cell death 3. Beyond DNA repair, DDB2 regulates chr11 remodeling, gene transcription, and cell cycle control 1. DDB2 also suppresses HIF1α expression in hypoxic tumors, reducing angiogenic responses 4. In cancer cells, KRAS mutations enhance platinum chemotherapy resistance by stabilizing DDB2 mRNA through m6A methylation, thereby increasing DNA repair capacity 5.