Caldesmon-1 is an actin filament stabilizing protein involved in the regulation of cell contraction. Binding of caldesmon-1 to actin is weakened by phosphorylation and by calmodulin in the presence of calcium. Caldesmon-1 is encoded by a single gene, which is spliced to generate a widely distributed low molecular weight form and a smooth muscle specific high molecular weight form (1,2). Caldesmon-1 is phosphorylated by the cyclin dependent kinase cdc2 and Erk1/2 MAP kinase, both of which prevent the activity of caldesmon-1 (3-5). Phosphorylation of caldesmon-1 by cdc2 is required for passage of cells through mitosis (6). Phosphorylation by Erk1/2 is important in regulating smooth muscle contraction (7). Caldesmon-1 activity may play a role in the formation of podosomes, adhesion complexes associated with the secretion of matrix metalloproteases, invasion, and metastasis (reviewed in 5).