The carboxylesterase Notum is a key negative regulator of the Wnt signaling pathway by specifically mediating the O-depalmitoleoylation of Wnt proteins.7, 8 The role of Notum in the mammalian central nervous system (CNS) has yet to be established although Notum is expressed and upregulated in endothelial cells in the hippocampus of APPPS1 mice and AD patients compared to control.9 The gene discussed is NOTUM; the disease is Alzheimer disease.