As a proof-of-concept, we used two substrates,α-synuclein and apoptosis-linked gene-2-interacting proteinX (ALIX), and enzymes UbE1, UbE2D3, and neuronal precursor cell-expresseddevelopmentally downregulated 4 (NEDD4)-family E3 ligases (NEDD4Land WW domain containing E3 ubiquitin protein ligase 2 (WWP2)); Figure 1A. Aberrant aggregationof α-synuclein is a hallmark of Parkinson’s disease.7,8 α-synuclein accumulated in the Lewy bodies of Parkinson’spatients is often mono- and diubiquitinated,9 perhaps due to the breakdown of its degradation pathways. Here, PDCD6IP is linked to Parkinson disease.