After summarising the different E3 ubiquitin–protein ligases, which have been suggested to use α-synuclein as a substrate, we focus on one group of them—the NEDD4 family, which has many additional PD-linked substrates—and support the idea that NEDD4 family members can be considered as therapeutic targets to treat PD. This evidence concerns the gene NEDD4 and Parkinson disease.