Ovarian differentiation relies on the accurate and orderly expression of numerous related genes. Forkhead box protein L2 (FOXL2) is one of the earliest ovarian differentiation markers and transcription factors. In sex determination, FOXL2 maintains the differentiation of the female pathway by inhibiting male differentiation genes, including SOX9 and SF1. In addition, FOXL2 promotes the synthesis of follicle-stimulating hormone and anti-Müllerian hormone to support follicle development. Mutations in FOXL2 are associated with numerous female reproductive diseases. A comprehensive and in-depth study of FOXL2 provides novel strategies for the diagnosis and treatment of such diseases. This review discusses the mechanism of FOXL2 in female sex differentiation and maintenance, hormone synthesis, and disease occurrence and reveals the role of FOXL2 as a central factor in female sex development and fertility maintenance. This review will serve as a reference for identifying novel targets of other regulatory factors interacting with FOXL2 in female sex determination and follicle development and for the diagnosis and treatment of female reproductive diseases.
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