At the endoplasmic reticulum (ER) membrane, 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (PLCD4) and phospholipase D4 (PLD4) hydrolyse phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) to inositol 1,4,5-trisphosphate (I(1,4,5)P3) and diacylglycerol (DAG). Both lipases are thought to require three Ca2+ ions per subunit for activity. PLD4 is attached to the ER membrane via its PH domain while its C2 domain binds to the PI(4,5)P2 in the membrane (Lee et al. 2004). Overexpression or dysregulated expression of PLCD4 may initiate oncogenesis in certain tissues through upregulation of ErbB expression and activation of ERK pathway. PLCD4 can therefore be a useful tumor marker for breast or testicular cancer tissues (Leung et al. 2004).