IZUMO1R (JUNO) is a folate receptor 4 protein essential for mammalian fertilization, expressed on the plasma membrane of oocytes 1. Its primary function is to serve as the receptor for sperm-surface IZUMO1, mediating species-specific gamete recognition 2. The IZUMO1:IZUMO1R interaction establishes critical cell-cell adhesion between sperm and egg 1, with JUNO's conserved surface-exposed tryptophan residue required for sperm binding 3. Unlike other folate receptors, JUNO lacks the folate-binding pocket and does not bind folate 3. While this adhesion event is necessary for fertilization, it is insufficient alone for membrane fusion 1. Clinically, IZUMO1R mutations are associated with human infertility; rare single nucleotide polymorphisms identified in patients with fertilization failure and polyspermy were absent in controls 4. Anti-JUNO antibodies completely block gamete fusion in human in vitro fertilization assays 1. JUNO expression levels fluctuate during oocyte maturation and are disrupted by environmental exposures (bisphenol A, phthalates, microplastics) that decrease fertilization rates 5. These findings establish IZUMO1R as indispensable for human reproduction and a potential target for fertility diagnostics and therapeutic interventions.