From a therapeutic perspective, the emergence of immune checkpoint inhibitors (ICIs) like pembrolizumab and nivolumab has revolutionized the treatment of microsatellite instability–high (MSI-H) or defective mismatch repair (dMMR) cancers, commonly linked to germline variants in MMR genes (e.g., MLH1, MSH2, MSH6, PMS2) (72, 73). Here, MSH6 is linked to cancer.