Elevated O-GlcNAcylation causes yes-associated protein (YAP) hyperactivation in cancer cells, and several proteins in the Hippo pathway, such as low density lipoprotein receptor related protein 6 (LRP6), large tumor suppressor kinase 2 (LATS2), and YAP, undergo O-GlcNAcylation, which eventually activates the Hippo pathway. The gene discussed is LRP6; the disease is cancer.