Chemerin chemokine-like receptor 1 (CMKLR1)

Chemerin chemokine-like receptor 1 (CMKLR1) is a G protein-coupled receptor highly expressed on innate immune cells such as macrophages, dendritic cells, and neutrophils. Its endogenous ligands include the adipokine chemerin and the specialized pro-resolving lipid mediator resolvin E1. CMKLR1 activation triggers diverse signal transduction pathways, resulting in chemoattraction, inflammation modulation, adipogenesis, angiogenesis, and glucose metabolism regulation. The receptor plays key roles in inflammatory diseases, metabolic disorders, some cancers, cardiovascular and neurodegenerative diseases, and may serve as a therapeutic target in multiple contexts. Selective antagonists like CCX832 and α-NETA, and agonists including chemerin-derived peptides and resolvin E1, have been investigated preclinically and in early clinical trials. The receptor’s dual regulatory effects on inflammation pose both therapeutic promise and safety challenges, especially regarding immune and metabolic balance.

Other names

Chemerin receptor 1Chemokine-like receptor 1ChemR23DEZ (murine homolog)Resolvin E1 receptor

Agonist binding (e.g., chemerin, resolvin E1) activates Gi/o protein pathway, inhibits adenylyl cyclase, increases intracellular calcium, activates ERK1 and NF-κB signaling. Antagonists block receptor activation, reducing downstream inflammatory or metabolic signaling.