IZUMO2 is an immunoglobulin-like type I membrane protein (~23 kDa) with dual roles in reproductive and cancer biology. In male reproduction, IZUMO2 is testis-enriched and expressed from puberty onward, localizing to the acrosomal region of sperm 1. It participates in sperm-oocyte interaction, as anti-IZUMO2 antibodies significantly reduce hemizona assay rates, indicating involvement in gamete fusion 1. IZUMO2 expression is reduced in teratozoospermic men and significantly downregulated in round spermatids of non-obstructive azoospermia patients, suggesting clinical relevance for male infertility diagnosis 12. Notably, 40% of immunoinfertile women developed circulating antibodies against IZUMO2 epitopes, implicating immune responses against this fertility antigen 3. Beyond reproduction, IZUMO2 exhibits pathological functions in cancer biology. It facilitates the cell-in-cell phenomenon whereby triple-negative breast cancer cells engulf regulatory T cells, promoting cancer cell survival 4. In colorectal cancer, IZUMO2 is a methylation-driven gene associated with poor prognosis, with protein expression at invasion fronts independently predicting shorter overall and progression-free survival 56. These findings establish IZUMO2 as both a potential biomarker for male infertility assessment and a prognostic indicator in solid tumors.