The mammalian sirtuin family, consisting of NAD+-dependent class III histone/protein deacetylases, has 7 members (Greiss and Gartner, 2009). The physiological activities and pathological associations of sirtuins have been subjects of intense interest, as these are key regulators of metabolic processes that often impinge on health, aging and lifespan (Chalkiadaki and Guarente, 2012; Houtkooper et al., 2012). Perhaps the least investigated of the sirtuins is SIRT7. Like its more illustrious family member SIRT1, SIRT7 is nuclear localized. More specifically, it is enriched in the nucleolus (Ford et al., 2006; Barber et al., 2012; Ryu et al., 2014). Functionally, SIRT7 was first described by Guarente's group to be associated with active ribosomal RNA genes (or rDNA), where it interacts with RNA polymerase I and positively regulate its transcription activity (Ford et al., 2006). SIRT7 also interacts directly with the rDNA transcription factor upstream binding factor (UBF), and is responsible for resuming rDNA transcription, suppressed during cell division, upon mitotic exit (Grob et al., 2009). Proteomics analyses indicate that SIRT7 is also associated with several nucleolus-localized chromatin remodeling complexes (Tsai et al., 2012) and is involved in multiple components of pathways regulating ribosome biogenesis and protein translation (Tsai et al., 2014). Other recent findings have also implicated a role for SIRT7 in regulating aspects of cell survival in multiple tissue/organ systems. Like SIRT1, SIRT7 deacetylates p53, and in this regard appears to be cardioprotective. Sirt7 knockout mice were shown to exhibit reduced lifespan with frequent development of heart hypertrophy and inflammatory cardiomyopathy (Vakhrusheva et al., 2008). SIRT7 also deacetylates the acetylated lysine 18 of histone H3, and together with its association with E26 transformed specific (ETS) domain containing transcription factor ELK4 and perhaps other tumor suppressor factors, appears to promote a state of malignancy (Barber et al., 2012).