Also, many studies showed that mutations in NAD+ binding site leads to loss of deacetylase activity of Sirt6 in human cancer cells (Kugel et al., 2015), human fibroblasts (McCord et al., 2009), and 293T cells (Klein et al., 2020), indicating that the NAD+ binding site in the Rossmann domain is responsible for the deacetylase activity of Sirt6. Here, SIRT6 is linked to cancer.