A comprehensive review of GPR84: A novel player in pathophysiology and treatment

G protein-coupled receptor 84 (GPR84), a member of the highly conserved rhodopsin-like superfamily, represents a promising target for therapeutic drug development. Its distinctive expression profiles in adipocytes, gut endocrine cells, and various myeloid immune cells underscore its critical roles in fundamental physiological processes, particularly in metabolic regulation and immune responses. Over the past two decades, emerging research has demonstrated that GPR84 regulates immune cell chemotaxis, phagocytosis, and inflammatory responses, playing a pivotal role in metabolic disorders, inflammatory diseases, and organ fibrosis. However, the precise molecular mechanisms by which GPR84 is involved in these diseases remain largely uncharacterized, highlighting a significant gap in our understanding. Medium-chain fatty acids (MCFAs) are considered potential endogenous ligands for GPR84. Furthermore, the development of synthetic agonists and antagonists have provided valuable pharmacological tools for analyzing the ligand-GPR84 complex structure and investigating the extensive biological functions of GPR84. Ongoing preclinical and clinical studies highlight the potential of targeting GPR84 in molecular therapies, although concerns regarding drug safety and specificity require further investigation.