Bioavailable and brain penetrating inhibitor of group I p21-activated kinases (IC50 values 8.25 nM, 39.5 nM, and 55.3 nM for PAK1, PAK2, and PAK3, respectively) with good selectivity over PAK4 (IC50 value 779 nM) FRAX486 rescues the dendritic spine abnormality and audiogenic seizures, and reduces autism-like phenotypes of hyperactivity and restrictive or repetitive behaviors in Fmr1 KO mice. Not only represents FRAX-486 a potential breakthrough in the research for a treatment of Fragile X syndrome (FXS), it was also found to ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence.