GPR84 is a G protein-coupled receptor primarily expressed in immune cells and gut endocrine cells that functions as a metabolite sensor for medium-chain fatty acids (C9-C14), with capric acid, undecanoic acid, and lauric acid being the most potent agonists 1. In innate immune cells, GPR84 acts as a pro-inflammatory receptor that promotes expression of inflammatory mediators (TNFα, IL-6, IL-12B) and enhances phagocytosis through AKT, ERK, and NF-κB signaling pathways 2. In neutrophils, GPR84 mediates chemotaxis, reactive oxygen species production, and degranulation via the LYN-AKT/ERK pathway, with functional cross-talk with formyl peptide receptors to regulate NADPH oxidase activity 3. Notably, GPR84 couples to distinct signaling proteins in different cell contexts; macrophages utilize Gα15-dependent signaling for pro-inflammatory responses while other cells employ Gαi coupling 4. Pathophysiologically, GPR84-mediated signals contribute to age-associated cognitive decline through bacterial metabolite-induced peripheral myeloid inflammation that impairs vagal afferent neuron function 5, and GPR84+ myeloid-derived suppressor cells induce CD8+ T cell senescence via p53 pathway activation, promoting tumor immune evasion 6. Additionally, GPR84 expression on macrophages enhances antibody-dependent cellular phagocytosis of cancer cells 7. These diverse roles establish GPR84 as a therapeutic target in metabolic disorders, inflammatory diseases, and cancer immunotherapy 8.