Two LIM motif-containing protein kinases (LIMK) have been identified, LIMK1 and LIMK2. These kinases contain two N-terminal LIM domains, a central PDZ domain, and a C-terminal Ser/Thr kinase domain. LIMK1 is highly expressed in brain, heart, and skeletal muscle, while LIMK2 exhibits the highest expression in placenta, liver, lung, kidney, and pancreas. LIMK1 is localized to the actin cytoskeleton and phosphorylates the actin binding/depolymerizing factor, cofilin. During Rho-induced neurite retraction, activation of ROCK leads to LIMK1 activation via phosphorylation at Thr508. In COS-7 cells, disruption of the second LIM domain or the PDZ domain increases LIMK1-induced aggregation of the actin cytoskeleton. In addition, a 32 kDa splice variant that contains only the N-terminus (dLIMK1) suppresses LIMK1 activity by interaction with the C- terminal kinase domain. In humans, deletion of LIMK1 has been implicated in Williams syndrome, a disorder that produces a distinct cognitive profile and vascular disease. Thus, LIMK1, and its splice variant dLIMK1, are thought to have important roles in the regulation of the actin cytoskeleton in a wide varitey of tissues.