PRKN and Parkinson disease: In particular, mutations in parkin represent one of the major causes of early-onset familial PD (Biskup et al., 2008; Kitada et al., 1998; Lesage and Brice, 2009); It was thus proposed that mutations in parkin, an E3 ubiquitin ligase which ubiquitinates and degrades a diverse array of substrates, would cause accumulation and aggregation of these substrates due to insufficient E3 ligase activity for ubiquitin-proteasomal dependent protein turnover (Kahle and Haass, 2004; Li and Guo, 2009; Sriram et al., 2005).