WEE2 is an oocyte-specific protein tyrosine kinase essential for regulating meiotic cell cycle progression in female gametes 1. The protein functions by phosphorylating CDK1 at tyrosine-15, thereby inhibiting CDK1 activity 2. During the germinal vesicle stage, WEE2 maintains meiotic arrest by preventing CDK1 activation, preserving oocytes in prophase I quiescence 2. Upon fertilization and oocyte activation, WEE2 also promotes metaphase II exit by inactivating maturation-promoting factor (MPF), enabling pronuclear formation and meiotic completion 2. Biallelic loss-of-function WEE2 variants cause oocyte maturation arrest and fertilization failure, representing a significant cause of female infertility 3. Identified variants include frameshift mutations, missense variants, and novel splicing mutations that impair WEE2 enzymatic activity 45. Functionally, WEE2 mutations reduce CDK1 phosphorylation capacity and pronucleus formation rates 6. Disease phenotypes span oocyte maturation arrest, fertilization failure, and early embryonic arrest with autosomal-recessive inheritance 13. Clinically, artificial oocyte activation using WEE2 complementary RNA or alternative MPF-inactivating agents can overcome fertilization failure in affected patients 2. Notably, mouse models with Wee2 deletion show only minor fertility effects, suggesting potential biological redundancy 7.