AS is a NDD which mainly arises from de novo mutations occurring in the maternal allele of the UBE3A gene, which encodes an E3 ubiquitin ligase.125 UBE3A is expressed biallelically during early neurodevelopment before being paternally silenced in mature neurons.126 The canonical function associated with UBE3A is to target specific proteins for proteasomal degradation through poly-ubiquitination. Here, UBE3A is linked to Neurodevelopmental delay.