PLD4

Lysosomal 5'->3' exonuclease that functions in nucleic-acid sensing by immune cells. Hydrolyzes phosphodiester bond in single-stranded RNA and DNA molecules, with a higher efficiency for molecules with 5' uridine and guanosine residues. It can stall at certain sites and does not necessarily proceed to complete exonucleolytic degradation, thereby producing nucleoside 3'-monophosphates but also 5'-end 5'-hydroxy deoxyribonucleotide/ribonucleotide fragments. Through the processing of self and exogenous RNA and DNA molecules, provides molecular signals to toll-like receptors (TLRs) in innate immunity. Partially redundant with PLD3, it cooperates with the RNase T2/RNASET2 to generate 2',3'-cGMP and cytidine-rich RNA fragments that occupy the two TLR7 ligand-binding pockets, to trigger receptor activation and signaling. Can exert polynucleotide phosphatase activity toward 5'-phosphorylated single-stranded DNA substrates although at a slow rate. Could play a role in phagocytosis of activated microglia (By similarity)..

Function from UniProtKB (Q96BZ4), read 2026-09-23. CC BY 4.0.