FRAX486 is an inhibitor of group I p21-activated kinases (PAKs; IC50s = 8.25, 39.5, and 55.3 nM for PAK1, PAK2, and PAK3, respectively). It is selective for group I PAKs over PAK4, a group II PAK (IC50 = 779 nM). FRAX486 (20 mg/kg) reverses decreases in the mean density of apical dendritic spines in the temporal cortex in the Fmr1-/- mouse model of fragile X syndrome. It completely abolishes audiogenic seizures, hyperactivity, and stereotypical movements in Fmr1-/- mice when administered at a dose of 30 mg/kg. FRAX486 prevents adolescent cortical dendritic spine loss and rescues prepulse inhibition deficits in a Disc1 knockdown mouse model of schizophrenia.