Abstract: Human Genetic studies result in identification of causative genes in Parkinson’s Disease (PD). The pathophysiological function of these genes remains largely unknown. During the past decade, we focus on dissecting genetic and epigenetic controls of PD pathogenesis. In this presentation, we will focus on how PD associated genes functions in cells and animal models and their potential link to PD pathogenesis. Our studies suggest that multiple PD associated genes functionally collaborative to regulate protein and cellular organelle quality control. We also identify PD associated gene ATP13A2 as an essential component to mediate fusion of autophagosome and lysosome. However, our study indicate that autophagy participates in PD but is not essential for initiation of PD. Interestingly, mitochondrial dynamics is potentially dysregulated in the early stage of pathogenesis. Our finding opens a new direction of PD research and design of clinical diagnosis and treatment.