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The long term goal of our research is to elucidate the molecular mechanisms by which proteins are targeted to specific and distinct compartments. We focus on the Rab GTPases that are master regulators of membrane trafficking. A molecular understanding of membrane traffic has broad implications for our understanding of growth control in cancer, receptor trafficking errors in heart disease, regulation of insulin secretion in diabetes and synaptic vesicle biogenesis and transport in neurological disorders. LRRK2 that is hyperactive in some types of Parkinson's Disease specifically phosphorylates Rabs--we want to understand how this is linked to disease. We have found that phosphorylation of Rab10 blocks primary cilia formation in culture and in certain brain regions and we would like to understand how this leads to Parkinson's disease. We also study the NPC1 protein that is essential for cholesterol transport in humans and can lead to Niemann Pick C disease when mutated.