NDE1 (nudE neurodevelopment protein 1) is essential for cerebral cortex development, functioning primarily in centrosome duplication, mitotic spindle formation, and neuronal progenitor division 1. NDE1 regulates the orientation of the mitotic spindle in cortical progenitors; perpendicular division orientation produces two proliferative progenitors, while parallel orientation yields one progenitor and one postmitotic neuron, directly controlling final neuron numbers and cortical layer composition 2. Mechanistically, NDE1 recruits and stabilizes LIS1 binding to dynein, promoting assembly of active dynein-dynactin-adaptor complexes essential for intracellular transport and nucleokinesis 3. NDE1 also acts as a RAB9A/B effector, tethering late endosomes to dynein for retrograde transport to the trans-Golgi network. NDE1 mutations and deletions cause severe neurodevelopmental disorders: homozygous or compound heterozygous NDE1 mutations result in lissencephaly 4 with microcephaly and microhydranencephaly, characterized by severe microcephaly, intellectual disability, and corpus callosum abnormalities 4. 16p13.11 duplications containing NDE1 are associated with developmental delay, intellectual disability, and autism spectrum disorder, with NDE1 identified as essential to the neurocognitive phenotype 5. These findings establish NDE1 as a critical regulator of brain size and cortical architecture through dynein-dependent mechanisms.