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However, the cellular and molecular mechanisms by which CKAP2L contributes to the pathogenesis of this syndrome remain largely unknown. Here, we generated a Ckap2l knockout mouse model to investigate the in vivo and cellular roles of CKAP2L. Interestingly, Ckap2l knockout mice show no overt developmental abnormalities, with the exception of reduced male fertility, evidenced by decreased sperm count, impaired motility, and abnormally elongated flagella. At the cellular level, CKAP2L is a bona fide microtubule-associated protein that localizes to microtubule-based organelles, including the centrosome, mitotic spindle, and ciliary basal body. Depletion of CKAP2L leads to shortened mitotic spindles and cytokinesis failure, resulting in multinucleation. Furthermore, we uncover a conserved function for CKAP2L as a negative regulator of primary cilium length; its loss markedly increases ciliary length in both human and mouse cells. Collectively, these findings position CKAP2L as a multifunctional regulator of microtubule-based organelles and suggest that Filippi syndrome can be classified as a \u2018centrosomopathy\u2019 arising from concurrent defects in cell proliferation and ciliary function.<\/jats:p>","DOI":"10.1093\/jmcb\/mjaf054","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T12:59:32Z","timestamp":1765285172000},"source":"Crossref","is-referenced-by-count":4,"title":["Filippi syndrome-associated CKAP2L modulates microtubule dynamics essential for mitosis and ciliary length regulation"],"prefix":"10.1093","volume":"18","author":[{"given":"Qian","family":"Lyu","sequence":"first","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University , Jinan 250014 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghao","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University , Jinan 250014 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3131-7804","authenticated-orcid":false,"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University , Jinan 250014 ,","place":["China"]},{"name":"State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University , Tianjin 300071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8595-8159","authenticated-orcid":false,"given":"Huijie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University , Jinan 250014 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Molecular Medicine, Key Laboratory of Cell and Biomedical Technology of Shandong Province, College of Basic Medicine, Jining Medical University , Jining 272067 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0307-0085","authenticated-orcid":false,"given":"Qingchao","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University , Jinan 250014 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"2026072906462774800_bib1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/dvdy.426","article-title":"Cilia kinases in skeletal development and homeostasis","volume":"251","author":"Abraham","year":"2022","journal-title":"Dev. 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