5'->3' DNA exonuclease which digests single-stranded DNA (ssDNA) (PubMed:30111894). Regulates inflammatory cytokine responses via the degradation of nucleic acids, by reducing the concentration of ssDNA able to stimulate TLR9, a nucleotide-sensing receptor (PubMed:30111894). Involved in phagocytosis of activated microglia (PubMed:22102906). Exonucleolytic cleavage in the 5'- to 3'-direction to yield nucleoside 3'-phosphates. Optimum pH is pH 5.5-5. Activation of microglia induces translocation of PLD4 from the nucleus to the phagosomes. Enriched in the white matter of early postnatal brains, as well as in splenic marginal zone cells (PubMed:21085684). Highly expressed in dendritic cells (DCs) and other myeloid cells, with lower expression in B cell (PubMed:30111894). First detected in cerebellum at postnatal day 0 (P0), increased with age and peaked at P7, and then rapidly decreased to adult levels by P21. Up-regulated by lipopolysaccharide (LPS) stimulation in microglia (PubMed:22102906). Increased expression in activated microglia and in the demyelinating lesions of adult brain (PubMed:22102906). Highly N-glycosylated. Deficient mice exhibit a phenotype of chronic activation of the immune system, with splenomegaly marked by elevated levels of interferon-gamma (IFN-gamma) (PubMed:30111894). PDL3 and PLD4 double-deficient mice are unable to survive beyond the age of 21 days due to severe liver inflammation (PubMed:30111894). Livers from double-knockout mice develop lethal hepatic autoinflammatory disease that could be prevented by a single allele of either PDL3 or PLD4 (PubMed:30111894). Belongs to the phospholipase D family. Exhibits no phospholipase activity, despite two HKD motifs.