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The plasma membrane acts as both a boundary and a site of exchange between the outside and the inside of a cell. The cytoskeleton plays essential roles in delineating membrane protein distributions, in defining structural and functional domains in the plasma membrane, and in regulating membrane protein, and ultimately, cell function. This volume reviews the regulation of membrane protein distribution, organization, and function at the plasma membrane by the cytoskeleton. Discussions also include the roles of cytoskeleton in the structural and functional organization of membranes and membrane proteins with emphasis on key problems, the current status of understanding, experimental approaches, and future directions.