The Protein Kinase C (PKC) family of homologous serine/threonine protein kinases is involved in a number of processes such as growth, differentiation, and cytokine secretion. At least eleven isozymes have been described. These proteins are products of multiple genes and alternative splicing. PKC consists of a single polypeptide chain containing four conserved regions (C) and five variable regions (V). The N-terminal half containing C1, C2, V1, and V2 constitutes the regulatory domain and interacts with the PKC activators Ca2+, phospholipid, diacylglycerol, or phorbol ester. However, the novel PKC (nPKC) subfamily members ( δ, ε, η, and θ isoforms) and the atypical PKC (aPKC) subfamily members (ζ, ί, and λ isoforms) are Ca2+ independent and lack the C2 domain. The aPKC members are unique in that their activity is independent of diacylglycerols and phorbol esters. They also lack one repeat of the cysteine-rich sequences that are conserved in cPKC and nPKC. The C-terminal region of PKC contains the catalytic domain. The PKC pathway represents a major signal transduction system that is activated following ligand-stimulation of transmembrane receptors by hormones, neurotransmitters, and growth factors. PKCλ shows the highest degree of amino acid homology with PKCζ (72%) and PKCλ mRNA is expressed in a variety of cells and tissues. The PKCλ protein kinase is capable of autophosphorylation and can be activated by phosphatidylserine, but not by other PKC activators such as diacylglycerols, Ca2+, or phorbol esters.