UBE3A (ubiquitin protein ligase E3A) is an E3 ubiquitin ligase that plays crucial roles in protein degradation and neurodevelopment 1. The gene is subject to genomic imprinting, with maternal-specific expression in neurons due to paternal silencing by antisense transcription 1. UBE3A functions in multiple cellular compartments including the proteasome, synapse, and nucleus, regulating protein stability and transcription 1. Loss of function of the maternally inherited UBE3A gene causes Angelman syndrome (AS), a severe neurodevelopmental disorder characterized by intellectual disability, speech impairment, ataxia, epilepsy, and distinctive behavioral features including frequent laughter 234. The syndrome results from four different molecular mechanisms: maternal deletion of chromosome 15-13, paternal uniparental disomy, imprinting defects, or maternally inherited UBE3A mutations 35. UBE3A disruption appears to inhibit synapse formation and experience-dependent synaptic remodeling, leading to functional defects in context-dependent learning and impaired maturation of hippocampal and neocortical circuits 4. Epilepsy occurs in 80-90% of AS patients, often presenting as pharmacoresistant seizures with underlying pathophysiology involving GABAergic dysfunction and thalamocortical hyperexcitability 6.