The role of G protein-coupled receptor 4 in inflammatory diseases and its potential clinical significance.

G protein-coupled receptor 4 (GPR4) is a dual ligand receptor that can be activated by both protons and lysophosphatidylcholine (LPC), which is a bioactive phospholipid. It plays a pivotal role in numerous physiological and pathological processes and is regulated by these two ligands through distinct mechanisms. Recently, there has been growing interest in the role of GPR4 in diseases characterized by an acidic microenvironment. This review aims to explore the specific signaling pathways through which protons and LPC regulate GPR4 in the inflammatory microenvironment and to clarify the distinct roles of these ligands in various diseases, including inflammation, atherosclerosis, and cancer. Additionally, the potential benefits and challenges of targeting GPR4 as a therapeutic strategy for these diseases are analyzed.