Phosphoinositide-specific phospholipase C (PLC) plays a crucial role in the initiation of receptor mediated signal transduction through the generation of the two second messengers, inositol 1,4,5-triphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. There are many mammalian PLC isozymes, including PLC ?1, PLC ?2, PLC ?3, PLC ?4, PLC?1, PLC?2, PLC ?1, PLC ?2 and PLCe. PLC? exists as four different isoforms. PLC ?1, a calcium signal amplifier, is activated by an atypical GTP-binding protein. In addition, PLC ?1 is an effector for GTP-binding protein transglutaminase II-mediated oxytocin receptor and ?1B-adrenoreceptor signaling. Mouse PLC ?1 is highly expressed in brain, heart, lung and testis. PLC ? is abnormally accumulated in autopsied brains with Alzheimer’s disease (AD), suggesting that it may play a role in the pathology of AD. PLC ?2 is markedly expressed in type II intestinal metaplasia and in the adenocarcinoma. When PLC ?2 is expressed in type I intestinal metaplasia, the metaplasia is generally considered benignant, yet evolves toward neoplastic transformation. Thus, PLC ?2 expression may be a possible marker of gastric malignant transformation.