MSH2 plays a crucial role in the DNA mismatch repair (MMR) pathway, which is essential for maintaining genomic stability by correcting errors that occur during DNA replication. MSH2 forms a heterodimer with MSH6 or MSH3 to recognize and bind to mismatched DNA, initiating the repair process. This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Additionally, the identification of additional homologs, PMS1 and PMS2, which are also implicated in MMR and mutated in HNPCC patients, underscores MSH2′s significance in cancer biology.