NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism (PubMed:22678360, PubMed:28334607). Acts as a negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway by promoting Wallerian degeneration, an injury-induced form of programmed subcellular death which involves degeneration of an axon distal to the injury site (PubMed:22678360). Wallerian degeneration is triggered by NAD(+) depletion: in response to injury, it is activated and catalyzes cleavage of NAD(+) into ADP-D-ribose (ADPR), cyclic ADPR (cADPR) and nicotinamide; NAD(+) cleavage promoting axon destruction (PubMed:22678360, PubMed:28334607, PubMed:31439792). Involved in the down-regulation of the tracheal immune response to Gram-negative bacteria (PubMed:22022271). This is likely by mediating Tollo signaling in the tracheal epithelium (PubMed:22022271). H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide NAD(+) = cyclic ADP-ribose + H(+) + nicotinamide Widely expressed in larval brains and adult brains. The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity. Severed axons in wild-type flies disappear completely within a week of injury, whereas axons of neurons homozygous for any one of the three loss-of-function alleles: l(3)896, l(3)4621, and l(3)4705 persist for several weeks after severing (PubMed:22678360). After infection with Gram-negative bacteria, the respiratory epithelium displays an over-active immune response with a greater increase in expression of Drs compared to wild-type larvae (PubMed:22022271). Belongs to the SARM1 family.