MMS22L is a DNA repair protein that functions as a component of the MMS22L-TONSL complex, which promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks 123. The complex is essential for maintaining genome integrity during DNA replication 4. MMS22L binds single-stranded DNA and facilitates RAD51 filament assembly following histone replacement and RPA eviction from DSBs 5. The TONSL-MMS22L complex recognizes H4K20me0, a histone mark specific to post-replicative chr6, enabling recruitment to damaged replication forks 6. Additionally, MMS22L functions in sister chr6 cohesion establishment through a pathway parallel to DSCC1-RFC, facilitating ESCO2 recruitment to replication forks 7. Clinically, MMS22L mutations are relevant to cancer biology. MMS22L deletion, observed in up to 14% of prostate cancers, sensitizes cells to PARP inhibitors by disrupting RAD51 loading; however, this response is TP53-dependent 8. Loss of MMS22L also impairs HR in BRCA2-deficient contexts, with the MMS22L-TONSL complex acting as a critical regulator of RAD51 activity 9. Beyond cancer, MMS22L mutations cause congenital erythroid disorders through disrupted erythropoiesis, with loss of MMS22L leading to proliferation arrest and p53 pathway activation 10.