The protein kinase C pathway is a major signal transduction system that is activated upon stimulation of transmembrane receptors by hormones, neurotransmitters, and growth factors. Key mediators in this pathway are increased intracellular free Ca2+ levels and formation of diacylglycerol (DAG). DGKθ (diacylglycerol kinase θ) restricts PKC activation through the phosphorylation of DAG molecules that contain an unsaturated fatty acid at the sn-2 position to produce phosphatidic acid (PA). DGKθ contains several regions that are found in signaling molecules where they function in lipid-protein and protein-protein interactions. A C-terminal catalytic domain, three CRDs (cysteine rich domains), a PH domain, and an N-terminal proline/glycine rich domain are structural features of DGKθ. Six potential PKC phosphorylation sites lie between CRD3 and the PH domain. Cell-specific expression differentiate multiple isoforms of DGK. DGKθ is expressed primarily within the cerebellar cortex and hippocampus of the brain, but is also found in the small intestine and liver. The presence of the RA (Ras-associating) domain suggests that DGKθ may mediate activity of the Ras-like small GTP binding proteins.