Variants in genes that encode components of the UPS (e.g., PARK2, UCHL1, FBXO7) and ALP (e.g., LAMP2A, PARK9) or directly affect alpha-synuclein (i.e., SNCA) can impair its degradation, leading to accumulation and aggregation of the protein, which is toxic to neurons and further leads to PD or other synucleinopathies [117,118]. The gene discussed is PRKN; the disease is Parkinson disease.