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Abbreviations: Gα, α-subunit of heterotrimeric G-protein; PKC, protein kinase C; PLD, phospholipase D; PtdIns(4,5)P 2 , phosphatidylinositol-4,5-bisphosphate. * To whom correspondence should be addressed.Abstract⎯Phospholipase D (PLD) catalyzes hydrolysis of phospholipids with production of phosphatidic acids, which often act as secondary messengers on transmission of intracellular signals. This review summarizes data of various leading laboratories on specific features of organization and regulation of PLD activity in plant and animal cells. The main structural domains of PLD (C2, PX, PH), the active site, and other functionally important parts of the enzyme are considered. Regulatory mechanisms of PLD activity are characterized in detail. Studies associated with molecular design, analysis, and synthesis of new nontoxic substances capable of inhibiting different PLD isoenzymes in vivo are shown to be promising for biotechnology and medicine.

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