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). Here, PRKN is linked to Parkinson disease.