Based on work showing that inhibition of the Wg divergent canonical target GSK3β/Shaggy is a promising FXS therapeutic treatment (Klein and Melton, 1996; Stambolic et al., 1996; McBride et al., 2005; Choi et al., 2010; Mines and Jope, 2011), we hypothesize that overabundant synaptic Dlp sequesters Wg ligand, inhibiting Wg signaling, and therefore the activity-dependent suppression of GSK3β/Shaggy. The gene discussed is GSK3B; the disease is fragile X syndrome.