Attenuated Glu signaling due to decreased mGluR5 availability is associated with increased excitotoxicity in many neurodegenerative disorders (Lewerenz and Maher, 2015; Crabbé et al., 2019) and may contribute to calcium dysfunction as well as downstream cdk5-ATM dysregulation in FXTAS. Here, CDK5 is linked to fragile X-associated tremor/ataxia syndrome.