Several hypotheses have been posited to explain synucleinopathy in PRKN-associated PD, including: (i) a gradual accumulation of α-syn with aging in these patients; (ii) a diminished capacity in late-onset PD patients to clear accumulated proteins; and (iii) the possibility that mutations result in only a partial loss of function in the PRKN ubiquitin E3 ligase (63). Here, PRKN is linked to Parkinson disease.