A recent study reported a novel role of nuclear SIRT2 in regulating Fzd receptors in AD, wherein nuclear SIRT2 was hyperactivated in AD and FoxO1 recruited SIRT2 to Fzd1 and Fzd7 promoters, leading to a reduction in H4K16ac deacetylation.752 These findings suggest that SIRT2 inhibition is an attractive target for ameliorating the pathological effects of AD. Here, FZD1 is linked to Alzheimer disease.