Meanwhile, an increasing body of evidence suggests that Homer protein homolog 1 (Homer1)-metabotropic glutamate receptor 5 (mGluR5) and downstream mammalian target of rapamycin (mTOR) signaling pathways affect the expression of proteins involved in the modulation of synaptic plasticity that may drive the pathophysiology of depression. This evidence concerns the gene GRM5 and major depressive disorder.