Mammalian phospholipase D physiological and pathological roles

Phospholipase D (PLD), a superfamily of signalling enzymes that most commonly generate the lipid second messenger phosphatidic acid, is found in diverse organisms from bacteria to humans and functions in multiple cellular pathways. Since the early 1980s when mammalian PLD activities were first described, most of the important insights concerning PLD function have been gained from studies on cellular models. Reports on physiological and pathophysiological roles for members of the mammalian PLD superfamily are now starting to emerge from genetic models. In this review, we summarize recent findings on PLD functions in these model systems, highlighting newly appreciated connections of the superfamily to cancer, neuronal pathophysiology, cardiovascular topics, spermatogenesis and infectious diseases.