The Silent Information Regulator (SIR2) family of genes is a highly conserved group of genes that encode nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases, also known as Class III histone deacetylases. The best characterized of these genes is Saccharomyces cerevisiae Sir2, which is involved in silencing of mating type loci, telomere maintenance, DNA damage response and cell aging. SirT1, the mammalian ortholog of Sir2, is a nuclear protein implicated in the regulation of apoptosis, cellular senescence, endocrine signaling, glucose homeostasis, aging, and longevity. SirT2, one of several mammalian Sir2 homologs, deacetylates alpha-tubulin on Lys40 and histone H4 on Lys16, and is implicated in cytoskeletal regulation and progression through mitosis. SirT2 protein is mainly cytoplasmic and is associated with microtubules and the HDAC6 tubulin deacetylase. SirT3 exists in human cells in two forms, including a full-length, nuclear (44kD) protein and a processed (28kD) p