MSH4 (mutS homolog 4) is a meiosis-specific protein essential for reciprocal recombination and proper chromosome 1 during meiosis 1. The protein functions as part of the MSH4-MSH5 (MutSγ) complex, which binds to branched recombination intermediates and associates with the MLH1-MLH3 (MutLγ) nuclease to facilitate crossover formation 2. MSH4 physically interacts with RAD51 and DMC1, key DNA strand-exchange proteins involved in homologous recombination, suggesting its role in early meiotic recombination machinery 3. Expression is restricted to reproductive tissues, with transcripts detectable only in testis and ovary 1. Pathogenic variants in MSH4 are associated with both male and female infertility. In females, MSH4 mutations cause premature ovarian insufficiency (POI), accounting for a subset of cases where genetic screening identifies causative variants 45. In males, MSH4 variants contribute to spermatogenic failure and primary infertility 6. The gene demonstrates clinical significance as part of genetic diagnostic panels for reproductive disorders, with identification of pathogenic variants enabling personalized medical management and genetic counseling for affected patients 57.