INTRODUCTION: Metabotropic glutamate receptor 4 (mGluR4) regulates disease by modulating neurotransmitter release and synaptic plasticity and has been implicated in various diseases, including neurodegenerative disorders and psychiatric conditions, where its dysregulation can impact synaptic function and neuronal signaling. AREAS COVERED: This review covers the patents and key literature concerning mGluR4 PAMs by utilizing the search engines: SciFinder, Google Patents, and PubMed from 2017 to 2024. It summarizes the key exemplified compounds, relevant SAR, and key biological data presented in the patents and primary literature. The key findings and potential path forward are also discussed. EXPERT OPINION: The mGluR4 receptor serves as a novel target for the treatment of neurodegenerative disorders (namely Parkinson's disease), multiple sclerosis, and chronic pain along with other brain disorders. Two compounds have been advanced to early-stage clinical trials from Prexton Therapeutics and Appello Pharmaceuticals. The first compound from Prexton failed due to efficacy and the Appello compound has yet to have results disclosed. The results from this trial will be an important test for whether future mGluR4 PAMs are advanced into clinical trials.