Cellular differentiation and morphogenesis rely on both cytoskeletal remodeling and transcriptional programs to drive cell fate decisions. Their coordination is critical for proper lineage progression, yet if and how cytoskeletal elements can regulate fate in the nucleus is largely unknown. To explore this comprehensively, we profiled the nuclear proteome of human and murine neural stem cells (NSCs). Cytoskeletal proteins were enriched among the most abundant nuclear components, with a predominance of microtubule (MT)-interacting proteins, including the MT-associated protein MAP1B. MAP1B mutations have been identified in patients with periventricular heterotopia (PH), linked to neuron migration deficits. We found that MAP1B translocates to the nucleus in NSCs, where it interacts with the BAF chromatin remodeling complex to regulate NSC identity and differentiation. Perturbing MAP1B cytoplasmic-to-nuclear balance in NSCs leads to the generation of ectopic neurons in the mouse cerebral cortex, as found in PH patients harboring MAP1B mutations. Patient iPSC-derived brain organoids show nuclear enrichment of mutant MAP1B resulting in enhanced BAF chromatin binding along with neuronal heterotopia. Thus, MAP1B acts as a novel nuclear regulator of NSC fate, highlighting the key role of cytoskeletal elements in the nucleus for fate specification, and how disruption of this process can lead to disease.