The mammalian silent information regulator 2 (SIRT2) is an NAD-dependent histone deacetylase with known roles in the regulation of the cell cycle. SIRT2 is also a tubulin deacetylase functioning as an early mitotic checkpoint, but its roles in regulating cytoplasmic microtubule dynamics were unknown. Novel findings now indicate that SIRT2 is specifically enriched in brain oligodendroglia, where it functions specifically in modulating the oligodendrocyte cytoskeleton during its differentiation and maturation.