Cyclic GMP-dependent protein kinases (protein kinase G, PKG, cGK) are the major receptors of intracellular cGMP. These serine/threonine kinases mediate a plethora of physiological responses. Members of this family include cGKI?, cGKI?, and cGKII, and each member contains a leucine zIPer motif at the N-terminus. cGKI is thought to control the contractility of vascular muscle, the permeability of endothelial cells, and to inhibit platelet aggregation. It phosphorylates and thereby inhibits nitric oxide synthase. cGKII plays a key role in the regulation of the intestinal ion transport system, as well as inhibiting renin secretion in kidneys. Deregulation of cGMP kinase family members could be a factor in various human diseases.