In addition, considerations need to be made in light of recent human studies using positron emission tomography (PET) after administration of a novel specific mGluR5 PET ligand, 3-[18F]fluoro-5-(2-pyridinylethynyl) benzonitrile ([18F]FPEB), which showed reduced mGluR5 availability and distribution in humans with FXS (Brašić et al., 2021, 2022; Mody et al., 2021) either reflecting mGluR5 high occupancy, as a result of a hyperexcited network, or mGluR decreased protein expression. Here, GRM5 is linked to fragile X syndrome.