CMKLR1 (Chemerin Chemokine-like Receptor 1) is a G protein-coupled receptor primarily expressed on innate immune cells including macrophages, dendritic cells, and natural killer cells, as well as on vascular smooth muscle cells and adipocytes 1. The receptor binds chemerin, a multifunctional adipokine that requires proteolytic activation to exert biological functions 1. CMKLR1 signaling regulates diverse physiological processes including immune cell chemotaxis, calcium signaling, and lipid metabolism 2. Mechanistically, CMKLR1 controls triglyceride synthesis and fatty acid uptake through modulation of sterol regulatory element-binding protein 1c and CD36 scavenger receptor 2. The receptor also mediates resolvin E1-induced anti-inflammatory effects via PI3K/AKT/Nrf2 signaling, suppressing NLRP3 inflammasome activation and immune cell infiltration 34. CMKLR1 negatively regulates thermogenic beige adipocyte development and cold-induced thermogenesis by dampening IL-33/type 2 innate immunity signaling 5. In disease contexts, elevated CMKLR1 expression on pulmonary artery smooth muscle cells contributes to systemic sclerosis-associated pulmonary arterial hypertension pathogenesis through enhanced cell proliferation 6, while CMKLR1 expression on monocyte-derived macrophages serves as a biomarker for lung inflammation-fibrosis axis severity in idiopathic pulmonary fibrosis 7. CMKLR1 inhibition represents a potential therapeutic strategy for lipid-dependent cancers and obesity-related metabolic disorders.