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This review synthesizes current evidence on the origins, detection, functional consequences and disease relevance of neural somatic mosaicism. We find that somatic variants\u2014including single\u2010nucleotide variants, copy\u2010number variations, mobile element insertions, structural rearrangements and aneuploidies\u2014arise through distinct molecular mechanisms such as replication errors, oxidative stress, defective DNA repair and transposable element activity, each leaving characteristic mutational signatures. The developmental timing of mutations is the primary determinant of their clonal distribution and functional impact: early mutations generate widespread clones, whereas later events produce localized or single\u2010cell mosaics. We demonstrate that even small populations of mutant neurons can disrupt network dynamics when key signalling pathways are affected, as shown in mTOR\u2010related cortical malformations where non\u2010cell\u2010autonomous mechanisms drive epileptogenesis. Our analysis reveals that somatic mosaicism provides a unifying explanation for diverse neurological conditions, from focal epilepsies and neurodevelopmental disorders to late\u2010onset neurodegenerative diseases, including mechanisms invisible to conventional blood\u2010based genetic testing. We conclude that understanding the brain as a dynamic mosaic of billions of distinct genomes\u2014rather than a single\u2010genome organ\u2014is essential for accurate disease modelling, diagnostics and the development of targeted therapies.<\/jats:p>","DOI":"10.1111\/ejn.70689","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:01Z","timestamp":1789776001000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Somatic Mosaicism of the Brain: The Functional Implications of Post\u2010Zygotic Mutations to Neural Circuits"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9525-8896","authenticated-orcid":false,"given":"Maher Abdulrazzaq","family":"Al\u2010Hakeem","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy Al\u2010Nahrain University  Baghdad 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