Formyl peptide receptor 2 (FPR2) and Formyl peptide receptor 3 (FPR3) (FPR2/FPR3)

Formyl peptide receptor 2 (FPR2, formerly FPRL1) and Formyl peptide receptor 3 (FPR3, formerly FPRL2) are G protein-coupled receptors (GPCRs) that play pivotal roles in the regulation of the innate immune system [1, 7]. FPR2 is notably promiscuous, binding a wide array of ligands including lipid mediators like Lipoxin A4 and proteins like Annexin A1, which trigger pro-resolving and anti-inflammatory pathways [9, 18]. Conversely, it can also bind pro-inflammatory ligands such as Serum Amyloid A, leading to a complex "switch" in biological function depending on the ligand environment [1, 11]. FPR3 is closely related and expressed on cells like dendritic cells, though its specific physiological roles are less defined than those of FPR2 [12, 20]. These receptors are involved in the pathogenesis of various diseases, including atherosclerosis, Alzheimer's disease, and chronic inflammatory disorders, by modulating leukocyte trafficking and phagocytosis [14, 17]. Therapeutic strategies primarily target FPR2 with selective agonists to promote the resolution of inflammation, offering a novel approach to treating chronic inflammatory and cardiovascular conditions [8, 19]. Several small-molecule agonists and peptides, such as Laruprentag, are currently in various stages of clinical and preclinical development for these indications [8, 21]. The dual nature of FPR2 signaling makes it a challenging but promising target for precision medicine in inflammatory diseases [11, 22].

Other names

FPRL1FPRL2ALXLXA4RHM63FPRH1FPRH2FMLP-R-IIFMLPXFPR2AFMLPYN-formyl peptide receptor 2N-formyl peptide receptor 3

Agonism of FPR2 and FPR3 to promote the resolution of inflammation, inhibit neutrophil infiltration, and enhance macrophage efferocytosis.