Formyl peptide receptor 2 (FPR2) (FPR2)

The Lipoxin pathway is a critical component of the resolution phase of inflammation, primarily mediated by the Formyl peptide receptor 2 (FPR2), also known as the ALX receptor [1, 2]. FPR2 is a G protein-coupled receptor (GPCR) that exhibits complex pharmacology, binding both pro-resolving lipid mediators like Lipoxin A4 (LXA4) and Resolvin D1, as well as pro-inflammatory proteins like Serum Amyloid A (SAA) [2, 8]. Activation of FPR2 by lipoxins triggers signaling cascades that inhibit neutrophil recruitment, promote the clearance of apoptotic cells by macrophages (efferocytosis), and suppress the production of pro-inflammatory cytokines [3, 13]. This pro-resolving action is distinct from traditional anti-inflammatory mechanisms as it actively promotes the return to tissue homeostasis rather than simply blocking inflammatory initiators [3, 7]. Consequently, the lipoxin-FPR2 axis is a major therapeutic target for chronic inflammatory conditions, including cardiovascular disease, asthma, and neurodegeneration [8, 10, 16]. Drugs targeting this pathway, such as synthetic lipoxin mimetics and small-molecule FPR2 agonists, aim to resolve persistent inflammation without the side effects associated with broad immunosuppression [12, 13].

Other names

ALX receptorLipoxin A4 receptorALXRFPRL1Formyl peptide receptor-like 1HM63FMLP-R-II

Agonism of the FPR2 receptor to trigger pro-resolving signaling pathways, including inhibition of NF-kappaB and promotion of macrophage efferocytosis.