Gpr18, a G-protein-coupled receptor, belongs to the orphan class A family of the GPCR superfamily [2]. It has been suggested to be related to the endocannabinoid system, despite low sequence homology with cannabinoid receptors CB1R and CB2R [2]. Gpr18 may play roles in the migration and proliferation of cancer cells, macrophages, and other inflammation-associated immune cells, making it a potential target for inflammation, cancer, and analgesia therapy [1]. It is also involved in the resolution of inflammation, as it serves as the receptor for resolvin D2 (RvD2), a specialized pro-resolving mediator, and the RvD2/Gpr18 axis has a protective role in cardiovascular and metabolic diseases (CVMDs) such as atherosclerosis, hypertension, ischaemia-reperfusion, and diabetes [3,4,5].

In models of Duchenne muscular dystrophy, treatment with the Gpr18 agonist PSB-KD107 reduced inflammation, enhanced myogenesis, and improved muscle function, suggesting a therapeutic potential for this disorder [6]. Verbenalin, a component of Verbena in Xuanfeibaidu (XFBD) granules, alleviates acute lung injury induced by sepsis and IgG immune complex through direct binding to the Gpr18 receptor, inhibiting inflammatory signaling pathways and macrophage pyroptosis [7].

In conclusion, Gpr18 is a significant G-protein-coupled receptor involved in multiple biological processes, especially those related to inflammation and disease resolution. Studies using agonists in in vivo models like Duchenne muscular dystrophy and acute lung injury models have demonstrated its potential as a therapeutic target, highlighting its importance in understanding disease mechanisms and developing new treatments for related diseases.