Publisher Summary The actin-binding proteins–lipid interactions at the plasma membrane interface are considered via two aspects: first, generation of intracellular signals or second messengers—besides the classical receptor pathway—may involve mechanical stimuli that are produced by applying physical forces to the cell surface. This process of mechanotransduction allows function to follow a given form and represents a new concept. Second, it was proposed that the topogenesis of a membrane skeleton is determined by assembly limiting reaction steps. Hence, actin-binding protein–lipid interactions play a central role not only in mediating the anchorage of the cytoskeleton in the lipid layer, but also in defining a specific membrane topology. Moreover, the release of actin-binding proteins or certain lipids from their complex upon stimulation via receptors may represent a more direct way for a cell to trigger intracellular events through a transmembrane signaling mechanism.