XPC (Xeroderma Pigmentosum Complementation Group C) is a crucial DNA damage recognition protein that initiates global genome nucleotide excision repair (GG-NER) by detecting bulky DNA adducts, particularly UV-induced lesions 1. The protein functions as part of the XPC complex to sense DNA damage and transfer damaged DNA to the TFIIH core complex for verification and subsequent repair by XPF and XPG nucleases 1. Structurally, XPA positions the DNA lesion outside the TFIIH core complex, with XPB and XPD helicases working in opposition to facilitate lesion verification 1. Beyond DNA repair, XPC has multifaceted cellular roles including involvement in DNA damage response, cell fate decisions, and interactions with p53, p21, ARF, and p16 that can drive cells toward apoptosis, senescence, or tumorigenesis 2. Loss-of-function mutations in XPC cause xeroderma pigmentosum group C (XP-C), characterized by extreme photosensitivity and dramatically increased skin cancer risk due to accumulation of unrepaired UV damage 3. XPC-deficient cells exhibit impaired DNA repair capacity, reduced proliferative capacity, and abnormal inflammatory responses 3. Polymorphisms in XPC, particularly Lys939Gln, are associated with increased cancer susceptibility across multiple cancer types 4.