SLX1A (structure-specific endonuclease subunit SLX1A) is a catalytic component of the SLX1-SLX4 endonuclease complex that functions in DNA repair and telomere maintenance. As a structure-specific endonuclease, SLX1A catalyzes the resolution of complex DNA structures including Holliday junctions and stalled replication forks, contributing to homologous recombination repair, double-strand break processing, and telomeric D-loop disassembly 1. SLX1A mechanistically interacts with SLX4 and associates with critical DNA repair proteins including ERCC1-XPF, PLK1, and TOPBP1 to maintain DNA repair complex stability 2. The protein plays roles in both promoting and negatively regulating telomere maintenance pathways, including participation in t-circle formation and telomere lengthening mechanisms 1. Clinically, elevated SLX1A expression correlates with poor survival outcomes in prostate cancer and contributes to PARP inhibitor resistance in homologous recombination-deficient tumors 2. SLX1A knockdown restores olaparib sensitivity by disrupting SLX4-mediated DNA repair complexes, suggesting therapeutic potential 2. SLX1A mutations have been identified in colorectal neuroendocrine tumors, indicating broader cancer relevance 3. Additionally, elevated SLX1A expression in chr16 lymphocytic leukemia B-cells correlates with increased telomeric sister chr16 exchange, implicating SLX1A in alternative telomere maintenance mechanisms 1.