Interestingly, a missense mutation in the retromer VPS35 subunit (OMIM #601501) causes an autosomal dominant form of Parkinson disease [50,51], and although the precise molecular mechanism is still unclear, it seems likely that cargo missorting is a key contributing factor in both AP-5/SPG11/SPG15-related HSP and VPS35-related parkinsonism. The gene discussed is AP5B1; the disease is hereditary spastic paraplegia.