While pre‐clinical studies on pharmacological inhibition of mGluR5 in FXS mice have had successes (Richter et al., 2015), clinical trials using negative allosteric modulators have failed to date (Berry‐Kravis et al., 2016) possibly due to tolerance being developed, which has been observed in mice (Yan, Rammal, Tranfaglia, & Bauchwitz, 2005). Here, GRM5 is linked to fragile X syndrome.