Thus, PLD3 and PLD4 are novel nucleases working together in the endolysosomes of innate immune cells to prevent endogenous ssDNA sensing by TLR9 and thus the development of inflammatory syndromes (Figure 3), but further investigation is needed to address the relevance of PLD3/4 in humans and how they may contribute to specific autoimmune disorders (117–119). Here, PLD3 is linked to autoimmune disease.