TMEM95 is a sperm acrosomal membrane protein essential for mammalian fertilization 1. It functions as a receptor-binding protein that facilitates sperm-egg membrane fusion through a receptor-mediated interaction with the egg surface 1. Structurally, TMEM95 contains an evolutionarily conserved, positively charged region that serves as a putative receptor-binding surface; mutations in this region ablate egg-binding activity 1. During fertilization, TMEM95 operates within a phagocytosis-like engulfment process called SEAL (sperm engulfment activated by IZUMO1-JUNO linkage), where it acts as one of several essential fusogenic factors alongside DCST1/2, SPACA6, and FIMP 2. Knockout studies in mice demonstrate that TMEM95-deficient sperm can bind eggs but fail to fuse, establishing its critical role in the fusion step rather than initial adhesion 1. Clinically, a nonsense mutation (c.483C>A, p.Cys161X) in bovine TMEM95 causes severe male subfertility with only 1.7% insemination success, demonstrating that TMEM95 integrity is required for normal reproductive performance 3. In humans, environmental exposure to polystyrene microplastics downregulates TMEM95 expression, potentially impairing sperm functionality 4. TMEM95 represents a key molecular determinant of gamete fusion and male fertility.