Interestingly, so far, in none of the single knockout mice for these E3 ubiquitin–protein ligases has a clear PD phenotype such as α-synuclein accumulation or midbrain dopaminergic cell death, been described, neither in mice deficient for parkin [186], SIAH1a [187], SIAH1b [188], SIAH2 [189], CHIP [190], FBXL5 [191], ITCH [192], SMURF1 [193,194], SMURF2 [194], WWP1 [195], WWP2 [196], NEDD4-1 [197], nor NEDD4-2 [198]. This evidence concerns the gene PRKN and Parkinson disease.