There has been a concerted effort to repurpose mGluR5 NAMs for the treatment of FXS where these drugs rescue disease phenotypes in multiple preclinical models and have been safely tested in clinical trials (Gravius et al., 2010; Michalon et al., 2012; Scharf et al., 2015; Berry-Kravis et al., 2017). Here, GRM5 is linked to fragile X syndrome.