CUX2 is a transcription factor that plays crucial roles in neuronal development and function, particularly in upper cortical layers. The protein regulates neuronal proliferation, dendrite development, and synapse formation through sequence-specific DNA binding 1. During human brain development, CUX2 is expressed in transient compartments including the marginal zone and subplate neurons, marking critical histogenetic events during corticogenesis 2. In mature cortex, CUX2 specifically influences apical dendrite development in layer II-III neurons, complementing CUX1's effects on basal dendrites 3. Loss of CUX2 function leads to facilitation of excitatory synaptic transmission from entorhinal cortex to hippocampus and increased seizure susceptibility 1. The gene is associated with epileptic disorders, with multiple missense variants identified in temporal lobe epilepsy patients 1 and established links to developmental and epileptic encephalopathy 67. In pathological contexts, CUX2-expressing projection neurons show selective vulnerability in multiple sclerosis lesions 4 and exhibit transcriptomic changes in epilepsy 5. Beyond neurological functions, CUX2 also demonstrates tumor suppressor activity in certain cancers by regulating downstream transcriptional targets 67.