Since the identification of the first HECT (E6-AP in Angelman syndrome; AS) and RING (Parkin in juvenile form of Parkinson disease) E3 ligases (Kishino et al., 1997; Matsuura et al., 1997; Kitada et al., 1998), 42 additional players are shaping the diversified landscape of E3 types in the origin of neurological diseases (Figure 1B). This evidence concerns the gene UBE3A and nervous system disorder.