Abstract

The type II phosphatidylinositol 4-kinases produce the lipid phosphatidylinositol 4-phosphate and participate in a confusing variety of membrane trafficking and signaling roles. This review argues that both historical and contemporary evidence supports the function of the PI4KIIs in numerous trafficking pathways, and that the key to understanding the enzymatic regulation is through membrane interaction and the intrinsic membrane environment. By summarizing new research and examining the trafficking roles of the PI4KIIs in the context of recently solved molecular structures, I highlight how mechanisms of PI4KII function and regulation are providing insights into the development of cancer and in neurological disease. I present an integrated view connecting the cell biology, molecular regulation, and roles in whole animal systems of these increasingly important proteins. The type II phosphatidylinositol 4-kinases are versatile mediators of membrane trafficking, controlling pathways that impact on disease. Recent advances suggest that the membrane lipid environment regulates enzyme activity and that the complexity of trafficking routes can be explained by the ability of these kinases to promote membrane trafficking in different directions.