Although further studies will be needed to understand the differential roles of UBQLN2 in regulating normal, post-translationally modified, and mutant forms of α-syn, our results here defining UBQLN2 as a regulator of pS129 α-synuclein point to UBQLN2 as a potentially important modifier of synucleinopathies and as a component of altered proteostasis in neurodegenerative disease. The gene discussed is SNCA; the disease is synucleinopathy.