Phospholipase D3, also known as PLD3, is a protein that in humans is encoded by the PLD3gene.[5][6] PLD3 belongs to the phospholipase Dsuperfamily because it contains the two HKD motifs common to members of the phospholipase D family, however, it has no known catalytic function similar to PLD1 or PLD2. PLD3 serves as a ssDNA 5' exonuclease in antigen presenting cells.[7] PLD3 is highly expressed in the brain in both humans and mice, and is mainly localized in the endoplasmic reticulum (ER) and the lysosome.
How APP processing is affected by PLD3 during AD still remains unclear, and its role in the pathogenesis of AD is ambiguous.[14][15] PLD3 may contribute to the onset of AD by a mechanism other than by influencing APP metabolism, with one proposed mechanism suggesting that PLD3 contributes to the onset of AD by impairing the endosomal-lysosomal system.[14] In 2017, PLD3 was shown to have an association with another neurodegenerative disease, spinocerebellar ataxia.[16]
^Zhang DF, Fan Y, Wang D, et al. (August 2016). "PLD3 in Alzheimer's Disease: a Modest Effect as Revealed by Updated Association and Expression Analyses". Molecular Neurobiology. 53 (6): 4034–4045. doi:10.1007/s12035-015-9353-5. PMID26189833. S2CID15660705.
^Jiao B, Liu X, Tang B, et al. (October 2014). "Investigation of TREM2, PLD3, and UNC5C variants in patients with Alzheimer's disease from mainland China". Neurobiology of Aging. 35 (10): 2422.e9–2422.e11. doi:10.1016/j.neurobiolaging.2014.04.025. PMID24866402. S2CID140208846.
