IZUMO1 is an essential sperm cell-surface protein that serves as a ligand for the egg receptor JUNO (IZUMO1R), mediating the initial recognition and adhesion between gametes required for fertilization 1. The protein exhibits a distinctive boomerang-shaped structure and undergoes major conformational changes upon JUNO binding 1. IZUMO1 localizes to the equatorial segment of the acrosome-reacted sperm and is post-translationally modified through N-linked glycosylation and phosphorylation at multiple sites, with phosphorylation regulating its subcellular relocalization during sperm maturation 2. The IZUMO1-JUNO interaction functions as a conserved fertilization complex across vertebrates, forming a trimeric complex with SPACA6 and TMEM81 that creates the binding site for divergent egg proteins 3. While this adhesion is necessary for fertilization, it is insufficient for membrane fusion, which requires additional proteins including DCST1/2, TMEM95, FIMP, and TMEM81 4. IZUMO1 knockout mice are healthy but infertile, establishing its critical role in reproduction 5. Recent evidence demonstrates that gamete fusion occurs via a phagocytosis-like mechanism termed SEAL (sperm engulfment activated by IZUMO1-JUNO linkage), where oocyte microvilli engulf spermatozoa following IZUMO1-JUNO binding 4. These findings have implications for developing immunocontraceptives and fertility treatments.