Dysregulation of astrocytic mGluR5 is increasingly implicated in the pathophysiology of neurodegenerative and psychiatric disorders including Alzheimer's disease (AD), Parkinson's disease (PD), depression, anxiety, and schizophrenia (SCZ) by promoting neuroinflammation, excitotoxicity, and synaptic dysfunction. This evidence concerns the gene GRM5 and early-onset autosomal dominant Alzheimer disease.