Afadin is a cell-cell adherens junction F-actin binding multidomain protein. Two splice variants of afadin have been described: l-afadin, which is ubiquitously expressed, and the smaller s-afadin, which is abundantly expressed in neural tissue. l-Afadin contains one PDZ domain near its middle followed by three proline-rich and one F-actin-binding region at the carboxyl-terminal. l/s-Afadin is localized to cell-cell junctions and binds several cytoplasmic proteins such as the small GTPase Ras, the tight junction protein ZO-1, and the vinculin binding protein ponsin/SH3P12.