Phospholipase D (PLD)

Phospholipase D is an enzyme superfamily defined by a conserved HKD domain catalytic motif and commonly characterized by the hydrolysis of phospholipids, especially phosphatidylcholine, to produce phosphatidic acid and a free head group like choline[1][2][3][4]. The two main human isoforms, PLD1 and PLD2, have highly similar tertiary structures with differing regulatory sequences and membrane orientations, and both play essential roles in membrane dynamics, signal transduction, and cellular communication[1][5]. Phospholipase D is implicated in pathological processes including oncogenesis, neurodegeneration, infection, and inflammation, making it a promising therapeutic target, with several small-molecule inhibitors in preclinical or early clinical development[5][9]. Isoforms exist in plants (PLDα, β, γ, δ), animals, and pathogens, highlighting a conserved biological importance[4]. Phospholipase D regulates many physiological processes, such as membrane trafficking, cytoskeletal organization, and cell migration, primarily through its generation of phosphatidic acid, which is a pivotal lipid signaling molecule[3][5][7].

Other names

PLDPLD1PLD2Phosphatidylcholine-hydrolyzing phospholipase Dplant PLDα, β, γ, δ

Inhibition of phosphatidic acid generation, down-regulation of PLD-mediated signaling pathways, and reduction of cell migration and proliferation.