Curriculum Vitae of WEE2 Kinase in Homeostasis and Diseases: A Systematic Review.

WEE2, an oocyte-specific kinase of the WEE family, is a core regulator of oocyte meiosis. It maintains germinal vesicle (GV) arrest and prevents premature meiotic resumption by phosphorylating cyclin-dependent kinase 1 (CDK1), thereby inhibiting maturation-promoting factor (MPF) activity. WEE2 also regulates exit from metaphase II (MII), ensuring orderly meiotic progression. Consequently, the functional integrity of WEE2 is essential for female reproduction. Homozygous or compound heterozygous mutations in the WEE2 gene represent a major genetic cause of total fertilization failure and primary infertility, as these mutations lead to reduced or abolished kinase activity, impair meiotic control, and disrupt oocyte maturation and embryonic development. This review systematically summarizes the protein structure, core functions, and mutation types of WEE2, along with its association with total fertilization failure and female primary infertility. It also highlights research advances in WEE2-targeted inhibitors and discusses the potential applications and future directions of WEE2 in the diagnosis and management of reproductive disorders.