α-Actinin belongs to the spectrin family of cytoskeletal proteins. It was first recognized as an actin cross-linking protein, forming an antiparallel homodimer with an actin binding head at the amino terminus of each monomer. More recently, α-actinin has been shown to interact with a large number of proteins involved in signaling to the cytoskeleton including those involved in cellular adhesion, migration, and immune cell targeting (1). The interaction of α-actinin with intercellular adhesion molecule-5 (ICAM-5) helps to promote neurite outgrowth (2). In osteoblasts, interaction of α-actinin with integrins stabilizes focal adhesions and may protect cells from apoptosis (3). Isoforms 1 and 4 of α-actinin, which are non-muscle isoforms, are present in stress fibers, sites of adhesion and intercellular contacts, filopodia, and lamellipodia. The muscle isoforms 2 and 3 localize to the Z-discs of striated muscle and to dense bodies and plaques in smooth muscle (1).