For more than a decade, our understanding of the molecular pathophysiology of FXS has been substantially advanced by the corroboration of “mGluR theory of FXS” in a wide range of experiments with a number of different mGluR5 inhibitors tested in both the Fmr1 KO mouse [49,50,51,52,53] and in the Drosophila models of FXS [54,55,56,57,58,59,60,61,62]. This evidence concerns the gene GRM5 and fragile X syndrome.