AbstractBackgroundG protein‐coupled receptor 39 (GPR39) is a transmembrane zinc receptor with two splice variants, which belongs to the G‐protein‐coupled receptor growth hormone‐releasing peptide family. Its expression is induced by zinc, which activates GPR39, and its activation mediates cell proliferation, ion homeostasis, and anti‐inflammatory, antioxidant, and other pathophysiological effects via different signaling pathways.AimsThe article reviews the latest literature in this field. In particular, the role of GPR39 in nervous system is discussed.Materials and methodsGPR39 can be a promising target in neurological diseases for targeted therapy, which will help doctors overcome the associated problems.DiscussionGPR39 is expressed in vivo at several sites. Increasing evidence suggests that GPR39 plays an important role as a neuroprotective agent in vivo and regulates various neurological functions, including neurodegeneration, neuroelectrophysiology, and neurovascular homeostasis.ConclusionThis review aims to provide an overview of the functions, signal transduction pathways, and pathophysiological role of GPR39 in neurological diseases and summarize the GPR39 agonists that have been identified in the recent years.