α-Actinin is a native actin cross-linking protein of the spectrin superfamily. In smooth muscle it forms a homodimer (~200 kDa total molecular mass). Four isoforms are known: isoforms 2 and 3 represent the “muscle” α-actinins localized in sarcomeres of skeletal and cardiac muscle, whereas isoforms 1 and 4 are “non-muscle” variants broadly expressed in multiple tissues.