Under physiological conditions, mGluR5 modulates synaptic transmission and might regulate both Hebbian and homeostatic plasticity.32–34 In pathological conditions, mGluR5 may contribute to maladaptive brain plasticity and persistent neurological dysfunctions35 as observed in Parkinson’s disease,36 fragile X syndrome (FXS)37 and Alzheimer’s disease.38 Negative allosteric modulators (NAMs) of mGluR5 have been in clinical trials as a potential therapeutic.35 This evidence concerns the gene GRM5 and Parkinson disease.