Lipid-modulating phosphodiesterase. Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity (PubMed:26095358). Acts as a negative regulator of Toll-like receptor signaling (PubMed:26095358, PubMed:27687724). Has in vitro phosphodiesterase activity, but the physiological substrate is unknown (PubMed:26095358, PubMed:27687724). Lacks activity with phosphocholine-containing lipids, but can cleave CDP-choline, and can release phosphate from ATP and ADP (in vitro) (PubMed:27687724). Binds 2 Zn(2+) ions per subunit. Interacts with TLR4, TLR7, TLR8 and TLR9. Macrophages and dendritic cells. Strongly up-regulated by TLR stimuli and interferon gamma. N-glycosylated. Mice display higher inflammatory responses in models of TLR-dependent peritonitis. Macrophages show enhanced responsiveness to TLR stimulation and a significant change in membrane fluidity and the global cellular lipid composition. Belongs to the acid sphingomyelinase family.