The UBE3A antibody is a crucial tool in studying the ubiquitin-protein ligase E3A (UBE3A), an enzyme encoded by the UBE3A gene located on chromosome 15q11.2-q13. This gene plays a vital role in the ubiquitin-proteasome system, regulating protein degradation and synaptic function. UBE3A is maternally expressed in neurons due to genomic imprinting, and its loss or mutation causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by intellectual disability, motor dysfunction, and seizures. Researchers use UBE3A antibodies to detect protein expression levels, localization, and functional interactions in cellular and animal models, aiding investigations into AS pathology and UBE3A's role in neurodevelopment. These antibodies are commonly employed in techniques like Western blotting, immunohistochemistry, and immunofluorescence. Specificity and validation are critical, as UBE3A shares homology with other E3 ligases. Recent studies also explore UBE3A's involvement in autism spectrum disorders and cancer, expanding its research relevance. Commercially available UBE3A antibodies are typically raised in rabbits or mice against epitopes within the N-terminal, HECT domain, or C-terminal regions, with validation in knockout models ensuring reliability. Their application continues to advance understanding of UBE3A's dual roles in neuronal health and disease.