Phospholipase D3 (PLD3)

Phospholipase D3 (PLD3) is a lysosomal enzyme belonging to the phospholipase D superfamily, with both nucleic acid (5'-3' exonuclease) and phospholipase D enzymatic activities. Unlike canonical PLD1 and PLD2 isoforms, PLD3 primarily degrades single-stranded DNA, especially mitochondrial DNA, in lysosomes to maintain nucleotide and lysosomal homeostasis, regulate autophagy, and prevent inappropriate activation of cytosolic DNA sensors such as cGAS-STING. Expressed highly in neuronal populations, PLD3 modulates amyloid precursor protein (APP) trafficking and amyloid beta peptide levels, with rare coding variants (e.g., V232M) linked to an increased risk of Alzheimer's disease and disrupted lysosomal function. Loss or mutation of PLD3 impairs lysosomal degradation, leads to substrate accumulation, activates innate immune pathways, and may contribute to neurodegenerative and inflammatory diseases[1][2][3][4][5].

Other names

5'-3' exonuclease PLD3HU-K4(S,S)-bis(monoacylglycero)phosphate synthase PLD3HindIII K4L homologHu-K4AD19HUK4SCA46choline phosphatase 3phosphatidylcholine-hydrolyzing phospholipase D3

Drugs or molecules modulating PLD3 would likely act via altering lysosomal enzyme activity, 5'-3' exonuclease function, or affecting APP processing and amyloid beta catabolism