Interestingly, paralleling the beneficial shift of the astrocyte reactive and inflammatory state, the metabolic dysfunctions were reverted in the SOD1G93A Grm5−/+ astrocytes, supporting the idea that the mGluR5 genetic downregulation can play a pivotal role in positively modulating astrocyte energy metabolism dysregulation in ALS. Here, GRM5 is linked to amyotrophic lateral sclerosis.