Phosphoinositide turnover is a well established mechanism of intracellular signal transduction. Sequential phosphorylation of phosphatidylinositol (PtdIns) results in PtdIns(4)P (PIP) and PtdIns(4,5)P2 (PIP2). Phospholipase C (PLC) hydrolyzes PIP2 to inositol (1,4,5)P3 (IP3) which stimulates release of intracellular Ca2+. PIP2 is generated by phosphorylation of PtdIns 5-kinases (PI5-K). These enzymes are divided into two types (I and II) based on their size and sensitivity to certain compounds. Three mammalian PI5-Ks, PI5-Kα, β, and γ of type I have been identified and a type II PIP5kα. Although the PI4-Ks are abundantly distributed throughout the cell, activity is found primarily in association with membranous structures. Members of this family contain a lipid kinase unique domain and a C-terminal catalytic domain.