PMS1 is a key component of the DNA mismatch repair (MMR) system, functioning as part of heterodimeric complexes with MLH1 and MLH3 proteins 1. The protein participates in the identification and repair of DNA mismatches that arise during replication, recombination, or chemical damage 2. PMS1 works within the broader MMR system alongside other proteins including MLH1, PMS2, MSH2, MSH6, MLH3, MSH3, and Exo1 to maintain genomic stability 2. Functionally, PMS1 plays a critical role in controlling somatic CAG repeat expansion, particularly in Huntington's disease pathogenesis, where PMS1 deficiency can drastically reduce or stop the expansion rate of mutant huntingtin CAG repeats in neurons 3. Clinically, PMS1 mutations have been identified in hereditary breast and ovarian cancer patients, highlighting its broader role in cancer predisposition 4. The gene has also been proposed as a modifier in Lynch syndrome, though its clinical significance in this context requires further clarification 5. Recent therapeutic research shows that targeting PMS1 through splice modulation can reduce pathogenic CAG repeat expansion, making it a potential therapeutic target for Huntington's disease 6.