NAMs of mGlu5 have shown promising results in preclinical models but many have progressed to phase II clinical trials for neurodegenerative diseases where they have failed to show efficacy in, including mavoglurant, basimglurant, STX107, fenobam, raseglurant, and AZD 2066 (Table 1). The gene discussed is GRM5; the disease is neurodegenerative disease.