DDB1 (damage-specific DNA binding protein 1) functions as a dual-role protein integrating DNA repair and protein ubiquitination. As a core component of the UV-DDB complex, DDB1 recognizes UV-induced DNA damage including cyclobutane pyrimidine dimers and 6-4 photoproducts, recruiting nucleotide excision repair machinery to damaged sites 123. DDB1 additionally serves as an essential scaffolding component of DCX (DDB1-CUL4-X-box) E3 ubiquitin ligase complexes that mediate substrate-specific protein degradation 45. In these complexes, DDB1 partners with variable substrate receptors (CRBN, DTL, DDB2, DCAF13) to target proteins for proteasomal degradation 678. Functionally, DDB1-containing ligases ubiquitinate histones at DNA damage sites to facilitate nucleosome remodeling and promote repair efficiency 910. The DDB1-CUL4A-CRBN complex represents a therapeutically exploitable target; thalidomide and derivative immunomodulatory drugs bind CRBN to redirect this ligase toward IKZF transcription factors and other neosubstrates, underpinning both teratogenic effects and anti-myeloma activity 116. Emerging molecular glue degraders exploit DDB1 complexes to selectively degrade disease-relevant proteins like cyclin K and p53, offering novel therapeutic strategies 12138. Disease associations include White-Kernohan syndrome and roles in cancer chemoresistance through mitochondrial dynamics regulation 14.