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The past several years have revealed that ER membrane contact sites (MCS) play a major role in regulating the biogenesis and dynamics of other cytoplasmic organelles. We have made the surprising discovery that MCS formed between dynamic ER tubules and multiple organelles including mitochondria, early and late endosomes, and even RNP granules define the position where these organelles undergo division. Our current goals are to identify the machinery and mechanism behind this ER-associated organelle division process. How can an ER tubule at a MCS trigger the division of another organelle and how is this process regulated in time? How can ER MCS regulate the division of so many different types of organelles? What is common and what is unique at the ER MCS that regulate organelle division. Here we will discuss our new data aimed at unraveling the molecular contributions of factors that localize to ER MCS and provide insight into their mechanistic roles.