NAD-dependent deacetylase sirtuin 2 is an enzyme that in humans is encoded by the SIRT2 gene. SIRT2 is an NAD+ -dependent deacetylase. Studies of this protein have often been divergent, highlighting the dependence of pleiotropic effects of SIRT2 on cellular context. The natural polyphenol resveratrol is known to exert opposite actions on neural cells according to their normal or cancerous status. Similar to other sirtuin family members, SIRT2 displays a ubiquitous distribution. SIRT2 is expressed in a wide range of tissues and organs and has been detected particularly in metabolically relevant tissues, including the brain, muscle, liver, testes, pancreas, kidney, and adipose tissue of mice. Of note, SIRT2 expression is much higher in the brain than all other organs studied, particularly in the cortex, striatum, hippocampus, and spinal cord.