Phosphatidylinositol transfer proteins (PITP) are abundant cytosolic proteins originally identified because of their ability to act in vitro as specific transporters of phosphatidylinositol or phosphatidylcholine between membranes. However, the cellular function of mammalian PITP has remained enigmatic till recently. Due to the development of reconstitution assays in cytosol-depleted cells, PITP was found to be an essential component for phospholipase C-mediated hydrolysis of PIP2 and for regulated exocytosis. The exact mechanism how PITP exerts its effects is not known but the PI binding/transfer activity of PITP can partly explain its cellular function. PITP would enable the local synthesis of PIP2 by delivering PI to specialized signaling sites.