Given the generally good quality of this preclinical work and the large volume of publications supporting the benefit of mGluR5 NAMs in mouse, fly, and rat models of FXS, the trial results reported here suggest that mGluR5-mediated responses in humans may have diverged evolutionarily from animal models and are not as important in mediating the neural effects of absence or marked reduction in FMRP or that the mGluR5 signaling system is differentially active in key brain regions in humans relative to rodents and thus less relevant to FXS. Here, FMR1 is linked to fragile X syndrome.