Abstract
The cytoskeletal protein vinculin is a major regulator of cell adhesion and attaches to the cell surface by binding to specific phospholipids. Structural, biochemical, and biological studies provided much insight into how vinculin binds to membranes, what components it recognizes, and how lipid binding is regulated. Here we discuss the roles and mechanisms of phospholipids in regulating the structure and function of vinculin and of its muscle-specific metavinculin splice variant. A full appreciation of these processes is necessary for understanding how vinculin regulates cell motility, migration, and wound healing, and for understanding of its role in cancer and cardiovascular diseases.