PLD4

5'->3' exonuclease that hydrolyzes the phosphodiester bond of single-stranded DNA (ssDNA) and RNA molecules to form nucleoside 3'-monophosphates and 5'-end 5'-hydroxy deoxyribonucleotide/ribonucleotide fragments (PubMed:30111894, PubMed:34620855, PubMed:38537643, PubMed:39423811). Partially redundant with PLD3, can cleave all four nucleotides displaying higher efficiency for ssDNA and RNA fragments initiated with uridine and guanosine residues and lower efficiency for cytidine-initiated substrates (PubMed:30111894, PubMed:34620855, PubMed:38537643, PubMed:39423811). As a result, it does not always degrade polynucleotides to the single nucleotide level, it can stall at specific sites sparing certain fragments from exonucleolytic degradation (PubMed:30111894, PubMed:34620855, PubMed:38537643, PubMed:39423811). Processes self and pathogenic ssDNA and RNA molecules that reach the endolysosomal compartment via phagocytosis or autophagy and may serve as 'danger' signals for recognition by innate immune receptors such as toll-like receptors (TLRs) (PubMed:38697119). Degrades mitochondrial CpG-rich ssDNA fragments to prevent TLR9 activation and autoinflammatory response, but it can cleave viral RNA to generate ligands for TLR7 activation and initiate antiviral immune responses (PubMed:38697119). In plasmacytoid dendritic cells, it cooperates with endonuclease RNASET2 to release 2',3'-cyclic guanosine monophosphate (2',3'-cGMP), a potent stimulatory ligand for TLR7 (PubMed:38697119). Produces 2',3'-cGMPs and cytidine-rich RNA fragments that occupy TLR7 ligand-binding pockets and trigger a signaling-competent state (PubMed:38697119). Can exert polynucleotide phosphatase activity toward 5'-phosphorylated ssDNA substrates although at a slow rate (PubMed:38537643). Transphosphatidylase that catalyzes the exchange with R to S stereo-inversion of the glycerol moiety between (S,R)-lysophosphatidylglycerol (LPG) and monoacylglycerol (MAG) substrates to yield (S,S)-bis(monoacylglycero)phosphate (BMP) (PubMed:39423811). Can synthesize a variety of (S,S)-BMPs representing the main phospholipid constituent of lysosomal intralumenal vesicle (ILV) membranes that bind acid hydrolases for lipid degradation (PubMed:39423811). Regulates the homeostasis and interorganellar communication of the endolysosomal system with an overall impact on cellular removal of dysfunctional organelles via autophagy as well as proper protein and lipid turnover. May play a role in myotube formation in response to ER stress (By similarity).