NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism ( ). 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 ( , ). Wallerian degeneration is triggered by NAD(+) depletion: in response to injury, SARM1 is activated and catalyzes cleavage of NAD(+) into ADP-D-ribose (ADPR), cyclic ADPR (cADPR) and nicotinamide; NAD(+) cleavage promoting cytoskeletal degradation and axon destruction (    ). Also able to hydrolyze NADP(+), but not other NAD(+)-related molecules . Can activate neuronal cell death in response to stress . Regulates dendritic arborization through the MAPK4-JNK pathway (By similarity). Involved in innate immune response: inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38 .
Subcellular locations: Cytoplasm, Cell projection, Axon, Cell projection, Dendrite, Synapse, Mitochondrion
Associated with microtubules.
Predominantly expressed in brain, kidney and liver. Expressed at lower level in placenta.