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We find that brain overgrowth begins early in development and can be suppressed with DYRK1A inhibitors. At the cellular level, the Mnb\/DYRK1A signaling pathway drives brain enlargement by inducing both neuronal hypertrophy and excessive proliferation of neural progenitors. We further demonstrate that Mnb up-regulates protein synthesis, and reducing Mnb activity or disrupting essential translational machinery restores brain size and improves locomotor coordination in the\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    FXS model. These data suggest that dysregulation of the Mnb\/DYRK1A signaling pathway contributes to brain overgrowth and aberrant protein synthesis in FXS. More broadly, our findings highlight that neurodevelopmental disorders such as FXS, Down syndrome, and autism share disruptions in common molecular pathways.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2517506123","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T19:07:46Z","timestamp":1771355266000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Up-regulation of Minibrain\/DYRK1A contributes to macrocephaly and brain overgrowth in a\n                    <i>Drosophila<\/i>\n                    model of fragile X syndrome"],"prefix":"10.1073","volume":"123","author":[{"given":"Mark","family":"Colt","sequence":"first","affiliation":[{"name":"Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California","place":["Los Angeles"]},{"name":"Neuroscience Graduate Program, University of Southern California","place":["Los 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