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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\u2019s 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\u2019s regulatory network may usefully provide insights into new therapeutic strategies in cancer and other human diseases.<\/jats:p>","DOI":"10.1177\/15578100251374589","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T13:06:46Z","timestamp":1759842406000},"page":"476-485","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["A Bird\u2019s-Eye View of the Wings Apart-Like Protein in Cell Biology and Implications for Disease and Therapeutics"],"prefix":"10.1177","volume":"29","author":[{"given":"Pathiyil Sajini","family":"Sekhar","sequence":"first","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Fahma","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhail","family":"Subair","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athira Perunally","family":"Gopalakrishnan","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prathik Basthikoppa","family":"Shivamurthy","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuvechha","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2319-121X","authenticated-orcid":false,"given":"Rajesh","family":"Raju","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(00)00376-2"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.37"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki070"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.01.024"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.108300"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2022.101956"},{"key":"e_1_3_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.059"},{"issue":"1","key":"e_1_3_5_9_1","first-page":"27","article-title":"[Research progress about Wapl gene]","volume":"41","author":"Cao L-X","year":"2010","unstructured":"Cao L-X, , Shen Z-F, , Pan W-W. 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