EXO1 is a highly conserved 5'→3' double-stranded DNA exonuclease that functions as a critical nuclease in multiple DNA repair and recombination pathways 1. In mismatch repair (MMR), EXO1 excises mismatch-containing DNA tracts directed by strand breaks and is essential for identifying and correcting replication errors 2. EXO1 also catalyzes long-range DNA end resection by degrading 5' DNA ends to generate 3' single-stranded DNA overhangs, a crucial early step required for homologous recombination repair of double-strand breaks 34. The BRCA1-BARD1 complex physically interacts with and upregulates EXO1 activity during end resection 4, while the CST complex suppresses EXO1-mediated resection 5. Disease relevance is substantial: defective MMR involving EXO1 dysfunction causes microsatellite instability, a major carcinogenic pathway in colorectal and hereditary nonpolyposis colorectal cancers 2. Loss of MLH1-mediated EXO1 regulation causes unrestrained DNA excision, activating the cGAS-STING immune pathway in dMMR tumors 6. Conversely, BRCA1-deficient tumors show elevated EXO1 expression, suggesting dependency on EXO1-mediated single-strand annealing for survival 7. EXO1 activity is tightly regulated through post-translational modifications to prevent excessive degradation and secondary lesions 1. EXO1 expression also correlates with prognosis and immunotherapy responsiveness in lung adenocarcinoma 8.