XPA is a 38-42 kDa zinc-finger DNA-binding protein that serves as a central scaffolding factor in nucleotide excision repair (NER), a critical DNA repair pathway 1. The protein initiates repair by recognizing and binding to various DNA lesions with different affinities, including UV-induced damage and bulky adducts 12. XPA functions as a molecular scaffold, organizing the assembly of NER repair complexes through protein-protein interactions with nearly all NER participants 34. During NER, XPA connects the XPB and XPD helicases, kinking DNA and positioning lesions for verification while stimulating helicase activities 2. The protein's damage recognition ability relies on a DNA-binding domain combining a zinc finger with a single-strand binding region that can infiltrate helix-destabilizing lesions 1. XPA deficiency causes xeroderma pigmentosum (XP), characterized by extreme UV sensitivity and >1000-fold increased skin cancer risk 56. Mouse models demonstrate that XPA knockout mice develop UV-induced skin tumors and show susceptibility to genotoxic carcinogens 56. Clinically, XPA expression levels and genetic polymorphisms have been associated with cancer susceptibility and chemotherapy response, making it a potential biomarker for platinum-based treatment outcomes 478.