ABRAXAS1 is a critical scaffold protein of the BRCA1-A complex that orchestrates DNA double-strand break (DSB) repair and genome stability. As a central component, ABRAXAS1 assembles BRCA1-A complex proteins and recruits BRCA1 to DNA lesion sites by recognizing lysine-63-linked ubiquitinated histones H2A and H2AX 1. The complex possesses deubiquitinase activity that removes lysine-63-linked ubiquitin from histones, regulating DNA repair pathway choice. Mechanistically, ABRAXAS1 interacts directly with BRCA1's BRCT domains; disruption of this binding shifts cells toward error-prone repair pathways including single-strand annealing and non-homologous end-joining 2. Heterozygous ABRAXAS1 mutations exhibit dominant-negative effects, causing reduced BRCA1 nuclear localization, impaired foci formation, and aberrant DNA damage responses despite preserved homologous recombination capacity 32. Germline ABRAXAS1 mutations confer breast cancer predisposition, particularly ovarian cancer risk, as demonstrated by functional assays showing abrogated BRCA1-ABRAXAS1 binding 4. Beyond DSB repair, ABRAXAS1 participates in broader cellular processes including mitotic checkpoint control and cell survival signaling 5. Beyond cancer, ABRAXAS1 variants are being identified in hereditary colorectal cancer screening, though their functional significance remains to be determined 6.