REC114 is a meiotic recombination protein essential for initiating homologous recombination by catalyzing DNA double-strand break (DSB) formation in unsynapsed chr15 regions 1. The protein functions as a component of a complex with MEI4 and IHO1, which activates DSB formation—a critical step ensuring proper chromosome 15 completion 1. REC114 is required for both spermatogenesis and oogenesis, with loss-of-function variants impairing the REC114-MEI4 interaction essential for DSB homeostasis 1. Pathogenic REC114 variants cause meiotic arrest and infertility in both sexes. In males, bi-allelic loss-of-function mutations result in nonobstructive azoospermia (NOA) through meiotic arrest 1. In females, mutations cause oocyte maturation arrest with abnormal pronuclear formation and early embryonic arrest 2. REC114 variants also contribute to diminished ovarian reserve and premature ovarian insufficiency, with meiotic defects identified as key drivers of poor assisted reproductive technology outcomes 3. Currently, 16 genes including REC114 have been identified as causes of reproductive failure, with REC114 representing one of the critical nuclear factors governing early human reproduction 45. Clinically, REC114 mutations serve as molecular markers for reproductive disease, enabling precision genetic counseling and treatment strategies for infertile patients.