The role of neuronal SphK1 in neuroinflammation. (A) Left, the role of SphK1 as an ATP-dependent lipid kinase that catalyzes the conversion of sphingosine to S1P, which in turn generates cellular responses including proliferation, angiogenesis, and migration. Right, the novel role of SphK1 as an acetyl-CoA dependent acetyltransferase with activity directed toward COX2, using sphingosine as the substrate. These enzyme activities induce SPM secretion, resulting in the resolution of neuroinflammation. (B) In neuroinflammatory environments, including those with the presence of Aβ, neuronal SphK1 decreases, which impairs S565 acetylation of COX2 and reduces SPMs secretion. Decreased SPM secretion in neurons reduced the number of microglia with a phagocytic phenotype.