In this mini-review, we highlight the function of metabotropic glutamate receptors (mGluRs), in particular mGluR3 and mGluR5, in reactive astrocytes and relate these to three degenerative CNS diseases: multiple sclerosis, Alzheimer’s disease and Amyotrophic Lateral Sclerosis. This evidence concerns the gene GRM5 and amyotrophic lateral sclerosis.