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Highlighting the significance of this pathway, several components are somatically mutated in focal cortical dysplasia (FCD), a neurological disorder characterized by intractable epilepsy. Supporting the functional impact of these variants, patient-derived SARM1 and RhoA mutations potentiate cilia loss, and a RhoA variant impairs cortical development. Conversely, SARM1 inhibition restores cilia in cells with FCD-associated alterations. Together, our work identifies a pathway for cilia disassembly, implicates aberrant pathway activation as a feature of FCD-associated mutations, and illustrates the potential of CRISPRa screening to provide insight into diseases caused by somatic mutations.<\/jats:p>","DOI":"10.1126\/sciadv.aeb7238","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:58:36Z","timestamp":1761760716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["A CRISPR activation screen reveals a cilia disassembly pathway mutated in focal cortical dysplasia"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4182-0753","authenticated-orcid":true,"given":"Shane D.","family":"Elliott","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, 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