Unlike other canonical members of the PLD family, PLD4 does not demonstrate phospholipase activity. Instead, PLD4 is known as an exonuclease that digests short ssDNA or ssRNA products in a 5' to 3' manner.[9][10] The optimum pH for PLD4 to digest single stranded nucleic acid substrate is around 4.4 to 4.8, which coincides with its acidic late-endosomal / lysosomal subcellular location.[8] Besides, it is also reported that PLD4, together with PLD3, participate in the synthesis of S,S-BMP, a phospholipid that is required for the degradation of lipids in lysosome.[11] As an endolysosomal protein, PLD4 along with PLD3 digest nucleic acid product inside the lysosome of phagocytes to modulate the activity of nucleic acid sensors such as TLR9, TLR7 etc. [9][10][12]
