mGluR1-expressing melanomas were demonstrated to have elevated levels of glutamate in their tumor microenvironment, established by an autocrine/paracrine loop that allows for the hyperactivation of the receptor, leading to the stimulation of the oncogenic MAPK and PI3K/AKT pathways in a manner that is independent of BRAF and NRAS mutations, as well as mGluR5 expression/activity (Figure 3) [28,39,45,50,52,52,53,54]. This evidence concerns the gene GRM5 and melanoma.