PRKN and Parkinson disease: Most early-onset autosomal recessive cases of PD are due to mutations in the gene encoding Parkin [25,26], an E3 ubiquitin-protein ligase involved in the ubiquitylation of a number of substrates (e.g. CDCRel-1, Pael R, synphilin, p38/JTV1/AIMP2, Eps15) and in various cellular mechanisms, including signaling pathways, synaptic transmission, proteasomal protein degradation and the autophagy of dysfunctional mitochondria [25,27].