Phospholipase D (, lipophosphodiesterase II, lecithinase D, choline phosphatase) (PLD) is an enzyme of the phospholipase superfamily. Phospholipases are widely occurring, and can be found in a wide range of organisms, including bacteria, yeast, plants, animals, and viruses. Phospholipase D’s principal substrate is phosphatidylcholine, which it hydrolyzes to produce the signal molecule phosphatidic acid (PA), and soluble choline. Plants contain numerous genes that encode various PLD isoenzymes, with molecular weights ranging from 90-125 kDa. Mammalian cells encode two isoforms of phospholipase D: PLD1 and PLD2. Phospholipase D is an important player in many physiological processes, including membrane trafficking, cytoskeletal reorganization, receptor-mediated endocytosis, exocytosis, and cell migration. Through these processes, it has been further implicated in the pathophysiology of multiple diseases: in particular the progression of Parkinson’s and Alzheimer’s, as well as various cancers.