A Bird's-Eye View of the Wings Apart-Like Protein in Cell Biology and Implications for Disease and Therapeutics.

Wings apart-like protein (WAPL) has emerged as a key player in maintaining genome integrity through its regulation of cohesin dynamics, which govern chromatin architecture and gene expression. WAPL mainly acts as a cohesin release factor and ensures proper chromosomal segregation during mitosis by promoting sister chromatid resolution. Owing to its prominent role in cell biology, WAPL dysregulation can cause genomic instability and disrupt chromosomal cohesion, leading to diseases such as cancer. The precise regulatory mechanisms controlling WAPL activity, including post-translational modifications and its broader implications in disease, remain incompletely understood. This expert review provides a comprehensive analysis and understanding of how WAPL activity is modulated throughout the cell cycle and how its dysfunction contributes to genome instability and disease. We discuss WAPL's molecular mechanisms, its interaction with associated proteins and regulation by antagonistic proteins, the role of post-translational modifications, and the implications of WAPL dysregulation in genome instability and oncogenesis. Future research examining WAPL's regulatory network may usefully provide insights into new therapeutic strategies in cancer and other human diseases.