SPATA16 (spermatogenesis associated 16) is essential for male fertility and spermiogenesis, with critical roles in acrosome formation during spermatogenesis 1. The gene is indispensable for sperm development; deletion of its fourth exon results in spermiogenic arrest in mice, though point mutations may have variable effects on fertility 1. SPATA16 mutations cause globozoospermia, a severe morphological sperm defect characterized by round-headed spermatozoa 2. Mutations in SPATA16 are associated with distinct phenotypes including double/multiple round-headed and multi-tailed sperm with elevated aneuploidy rates compared to other globozoospermia-causing mutations 3. Downregulation of SPATA16 is strongly associated with male infertility; promoter hypermethylation correlates with reduced SPATA16 expression in oligozoospermic, azoospermic, and IVF-failed samples 4. Genetic polymorphisms in SPATA16 (rs1515442) are associated with idiopathic azoospermia and oligospermia risk in affected populations 5. Additionally, SPATA16 variants have been identified as genome-wide significant loci for circulating PCSK9 concentrations, suggesting pleiotropic effects beyond reproductive function 6. SPATA16 mutations represent an important genetic cause of spermatogenic failure, contributing significantly to hereditary male infertility.