Mutations in parkin, a ubiquitin ligase, cause early-onset familial Parkinson's disease. There are many reports for the functions of parkin, but the precise mechanism of parkin/PARK2 in dementia with Lewy bodies and Parkinson's disease remains unknown. Our purpose was to investigate the cellular features of parkin in synucleionopathies, and the relationships to mitochondrial function and synuclein as well as neurodegeneration associated with demantia with Lewy bodies. We constructed the parkin plasmid in Tet-off system and establish the stable parkin over-expressing cell lines, and observed parkin cellular distribution and function by immunofluorescence. The cell viability and degeneration were analyzed by LDH, WST-1 and TUNEL assays. Synuclein metabolism related to autophagy was probed by immunoblot. The results showed Parkin wild type almost disperses in the cytoplasm, while the mutants take the shape of small granular structure to form the perinuclear inclusions causing mitochondrial dysfunction. Parkin WT regulates synuclein autophagy by mTOR pathway, promotes β-syn P123H into autophagolysosome and further degradation. Disease-causing mutations in Parkin increase the accumulation of β-syn P123H protein and enhance the autophagic cell death associated dementia with Lewy bodies.