{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:36:57Z","timestamp":1787315817337,"version":"build-2736575974"},"reference-count":204,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>The development and maintenance of the nervous system depend on a tightly regulated intracellular transport network in which kinesin superfamily (KIF) motor proteins drive microtubule-based delivery of synaptic vesicle precursors, organelles, mRNAs, and signaling components along axons and dendrites. Disruption of this machinery underlies a clinically heterogeneous spectrum of neurodevelopmental disorders (NDDs), including intellectual disability, epilepsy, autism spectrum disorder, microcephaly, malformations of cortical development, spasticity, and axonal neuropathy. Here, we synthesize current knowledge on how kinesin dysfunction shapes neurodevelopment. We outline the physiological roles of kinesins in neuronal polarity, organelle and mitochondrial positioning, synaptogenesis, and progenitor division, and survey principal disease-associated genes, including KIF1A, KIF5A, KIF7, KIF11, KIF2A, KIF5C, and emerging members such as KIF14, KIF15, and KIF16B. We detail how distinct pathogenic mechanisms, such as loss of motility, impaired cargo coupling, motor hyperactivity, mitotic spindle defects, and disrupted ciliary signaling, converge on shared cellular endpoints, and how tubulin isotypes and posttranslational modifications further modulate motor output. In this review, we discuss translational implications, including variant-resolved diagnosis and precision strategies to restore transport, dampen pathological hyperactivity, or stabilize the microtubule track. Collectively, these advances reframe kinesinopathies as mechanistically stratified disorders of neuronal transport.<\/jats:p>","DOI":"10.3390\/cimb48080837","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:09:32Z","timestamp":1787054972000},"page":"837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Traffic Jams in the Brain: How Kinesin Dysfunction Shapes Neurodevelopmental Disorders"],"prefix":"10.3390","volume":"48","author":[{"given":"Mohammad Sadegh","family":"Shams Nosrati","sequence":"first","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"},{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy"},{"name":"Department of Molecular Virology, Pasteur Institute of Iran, Tehran P.O. Box 13169-43551, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8557-1673","authenticated-orcid":false,"given":"Morteza","family":"Doustmohammadi","sequence":"additional","affiliation":[{"name":"Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran P.O. Box 14117-13135, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-2056","authenticated-orcid":false,"given":"Alireza","family":"Dostmohammadi","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biophysics, Faculty of Biology and Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, 45141 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3135-9879","authenticated-orcid":false,"given":"Armita","family":"Kakavand Hamidi","sequence":"additional","affiliation":[{"name":"Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran P.O. Box 14117-13135, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8638-1076","authenticated-orcid":false,"given":"Mahsa","family":"Boogari","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran P.O. Box 14618-84513, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2432-2114","authenticated-orcid":false,"given":"Zahra","family":"Hoseini Tavassol","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran P.O. Box 14117-13135, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakiba","family":"Khosravinejat","sequence":"additional","affiliation":[{"name":"Research Center, Alborz University of Medical Sciences, Karaj 3198764653, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Asgari","sequence":"additional","affiliation":[{"name":"Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Science, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morvarid","family":"Shafiei","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Pasteur Institute of Iran, Tehran P.O. Box 13169-43551, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Hesam","family":"Nemati","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Pasteur Institute of Iran, Tehran P.O. Box 13169-43551, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruccio","family":"Romano","sequence":"additional","affiliation":[{"name":"Genomic and Clinical Genetics Unit, IRCCS Istituto G. Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3097-0388","authenticated-orcid":false,"given":"Valeria","family":"Capra","sequence":"additional","affiliation":[{"name":"Genomic and Clinical Genetics Unit, IRCCS Istituto G. Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8247-4709","authenticated-orcid":false,"given":"Bruno","family":"Sterlini","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Universit\u00e0 di Genova, 16132 Genoa, Italy"},{"name":"IRCCS Azienda Ospedaliera Metropolitana, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Darbalaei","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biophysics, Faculty of Biology and Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, 45141 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Salehi","sequence":"additional","affiliation":[{"name":"West German Cancer Center, Department of Medical Oncology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-9717","authenticated-orcid":false,"given":"Mir Davood","family":"Omrani","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran P.O. Box 1985717443, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"},{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoha","family":"Kibar","sequence":"additional","affiliation":[{"name":"Azrieli Research Center of CHU Sainte Justine, University of Montreal, Montreal, QC H3T 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1097-0647","authenticated-orcid":false,"given":"Tatsuo","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Division of Advanced Genome Editing Therapy Research, Research Institute for Cell Design Medical Science, Yamaguchi University, Ube 755-8503, Japan"},{"name":"Department of Molecular and Cellular Physiology, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-7239","authenticated-orcid":false,"given":"Marcello","family":"Scala","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"},{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaaw9997","DOI":"10.1126\/science.aaw9997","article-title":"Axonal transport: Driving synaptic function","volume":"366","author":"Holzbaur","year":"2019","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.neuron.2014.10.019","article-title":"Axonal transport: Cargo-specific mechanisms of motility and regulation","volume":"84","author":"Maday","year":"2014","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Huertas, C., and Herrera, E. 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