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We generated\n                    <jats:italic>KCNQ1<\/jats:italic>\n                    knockout (KO) human induced pluripotent stem cells and differentiated them into neural stem cells (NSCs) and cortical neurons.\n                    <jats:italic>KCNQ1<\/jats:italic>\n                    -deficient NSCs show impaired neurite outgrowth, linked to reduced cell adhesion and disrupted neural cell adhesion molecule signalling, a phenotype reproduced by pharmacological KCNQ1 inhibition. Multi-omics and follow-up analyses reveal mitochondrial dysfunction, including reduced mitochondrial copy number and ATP synthase expression. KO cells also show impaired insulin signalling, with diminished insulin receptor gene expression and altered RAS-MAPK and PI3K-AKT pathways. In differentiated neuronal cultures,\n                    <jats:italic>KCNQ1<\/jats:italic>\n                    loss decreases synaptic activity and maintains an immature transcriptional profile. Together, these findings identify a role for KCNQ1 in regulating cell adhesion, mitochondrial function, insulin signalling, and neuronal maturation, expanding our understanding of processes that may contribute to neurological manifestations associated with\n                    <jats:italic>KCNQ1<\/jats:italic>\n                    -related disorders.\n                  <\/jats:p>","DOI":"10.1038\/s42003-026-11111-0","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:25:08Z","timestamp":1791919508000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["KCNQ1 disruption alters human neuronal development through mitochondrial and insulin signalling pathways"],"prefix":"10.1038","volume":"9","author":[{"given":"Dorothea","family":"Schall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baran E.","family":"G\u00fcler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siamand","family":"Alibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8577-6128","authenticated-orcid":false,"given":"Mahmudul","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6523-492X","authenticated-orcid":false,"given":"Naeem","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Widomska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8849-6260","authenticated-orcid":false,"given":"Claudio","family":"Acuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mair\u00e9ad","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"R\u00f6th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Blaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4668-1134","authenticated-orcid":false,"given":"Katalin","family":"Vincze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6814-2298","authenticated-orcid":false,"given":"Karin","family":"Burau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Macri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1225-4633","authenticated-orcid":false,"given":"Daniela","family":"Mauceri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Luzarowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0380-8139","authenticated-orcid":false,"given":"\u00c1gota","family":"Ap\u00e1ti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3641-012X","authenticated-orcid":false,"given":"J\u00e1nos M.","family":"R\u00e9thelyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Poelmans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-1508","authenticated-orcid":false,"given":"Gudrun A.","family":"Rappold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-6572","authenticated-orcid":false,"given":"Barbara","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Glennon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-2217","authenticated-orcid":false,"given":"Simone","family":"Berkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"11111_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0163-7258(01)00116-4","volume":"90","author":"J Robbins","year":"2001","unstructured":"Robbins, J. 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