ZMYND15 is a zinc finger protein that functions as a transcriptional repressor through interaction with histone deacetylases (HDACs) 1. It plays a critical role in spermatogenesis by regulating haploid gene expression and mediating interactions with key spermatogenic molecules including DPY19L2, AKAP4, FSIP2, and autophagy-associated protein SPATA33 to facilitate sperm individualization and cytoplasm removal 1. In mice, ZMYND15 deletion causes infertility due to nonobstructive azoospermia 2. Biallelic ZMYND15 variants cause male infertility with a phenotypic spectrum ranging from severe oligozoospermia to azoospermia, characterized by abnormal sperm morphology, reduced chr17 condensation, and nuclear aneuploidy 314. The biallelic pathogenic mutation frequency in infertile men is approximately 1.3% 1. Novel mutations identified include frameshift variants and missense variants predicted to be deleterious 3. Clinically, ZMYND15 expression levels in testicular tissue show diagnostic potential for predicting successful sperm retrieval in azoospermic men, with sensitivity of 90% and specificity of 60% 5. Additionally, seminal plasma cell-free mRNA of ZMYND15 and its target genes (TNP1, PRM1) may serve as noninvasive biomarkers for identifying focal spermatogenesis in nonobstructive azoospermia 6.