XRCC1 (X-ray repair cross complementing 1) is a scaffold protein that plays a critical role in DNA single-strand break (SSB) repair by facilitating the assembly of DNA repair protein complexes 1. The protein functions as a molecular scaffold that interacts with multiple enzymatic components including DNA kinase, phosphatase, polymerase, deadenylase, and ligase activities to accelerate repair of various DNA single-strand breaks 1. A key regulatory mechanism involves XRCC1's ability to negatively regulate PARP1 (poly(ADP-ribose) polymerase 1) activity during base-excision repair by recognizing and binding poly-ADP-ribose chains, specifically binding auto-poly-ADP-ribosylated PARP1 to limit its activity 2. When XRCC1 is deficient, excessive PARP1 activity occurs, leading to impaired transcriptional recovery following DNA base damage through aberrant recruitment of the ubiquitin protease USP3 2. This dysfunction can trigger neurological disease, as demonstrated in XRCC1-deficient patient fibroblasts and mouse neurons 2. XRCC1 mutations are associated with spinocerebellar ataxia, highlighting its clinical significance in preventing hereditary neurodegenerative disease 1. Recent research has also identified novel regulatory mechanisms, including lactylation-mediated nuclear translocation of XRCC1 for DNA damage repair in glioblastoma cells 3.