PLD3
Description
The PLD3 (phospholipase D family member 3) is a protein-coding gene located on chromosome 19.
PLD3 is a protein encoded by the PLD3 gene in humans. It belongs to the phospholipase D superfamily but lacks known catalytic activity like PLD1 and PLD2. PLD3 functions as a ssDNA 5' exonuclease in antigen-presenting cells. It is highly expressed in the brain, primarily located in the endoplasmic reticulum and lysosomes. PLD3 may regulate the lysosomal system, myogenesis, late-stage neurogenesis, inhibit insulin signal transduction, and influence amyloid precursor protein (APP) processing. Its involvement in the lysosomal system and APP processing, along with loss-of-function mutations, are linked to late-onset Alzheimer's disease (LOAD). However, some studies challenge this association. The precise effect of PLD3 on APP processing during AD remains unclear, and its role in AD pathogenesis is ambiguous. PLD3 might contribute to AD through a mechanism independent of APP metabolism, potentially by impairing the endosomal-lysosomal system. In 2017, PLD3 was associated with another neurodegenerative disease, spinocerebellar ataxia.
PLD3 is a 5'-3' DNA exonuclease that digests single-stranded DNA (ssDNA). It regulates inflammatory cytokine responses by degrading nucleic acids, reducing the concentration of ssDNA that can stimulate TLR9, a nucleotide-sensing receptor, in collaboration with PLD4. PLD3 may be important for myotube formation and plays a role in lysosomal homeostasis and the regulation of endosomal protein sorting.
PLD3 is also known as AD19, HU-K4, HUK4, SCA46.
