Protein kinase D (PKD), a serine/threonine kinase originally described as a novel PKC family member and termed PKCm, belongs to the calcium calmodulin superfamily of kinases. Three mammalian isoforms have so far been described - PKD1/PKCu, PKD2 and PKD3/PKCν; these isoforms show a high degree of homology, especially in their catalytic domain. PKDs are major targets for tumor promoting phorbol esters; they are activated via G protein-coupled receptors (GPCRs) and their activation is also dependent on PKC activation. PKDs have been implicated in numerous cellular functions, including signal transduction as well as cell survival, migration, differentiation, and proliferation. They are important regulators of secretory transport at the trans- golgi network. Of the three isoforms, PKD1 is the best characterized. It is involved in the regulation of Golgi function, cell proliferation and apoptosis and it mediates oxidative stress signaling regulating cellular detoxification and survival. PKD2 has been found to phosphorylate histone H1 more efficiently than aldolase in vitro.