Fpr2, also known as formyl peptide receptor 2 or ALX/FPR2, is a seven-transmembrane G-protein-coupled receptor. It is involved in sensing bacteria, modulating immune responses, and is crucial for various biological processes. Fpr2 can interact with ligands from different sources, and its functions are diverse, including controlling developmental and homeostatic signaling cascades, and mediating cell migration [4].

Genetic ablation of the Fpr2 gene has revealed its roles in multiple disease conditions. In a murine colitis model, Fpr2 was identified as a potential target for modulating LC3-associated efferocytosis to alleviate intestinal inflammation; blocking Fpr2 abolished the anti-colitis activity of the biased agonist columbamine [1]. In a preclinical model of influenza A virus (IAV) infections in mice, using Fpr2 antagonists protected animals from lethal infections as Fpr2-signaling otherwise led to increased viral replication and immune response dysregulation [2]. In female mice, Fpr2 knockout suppressed the progression of syngeneic pancreatic tumors, indicating its role in shaping an immune-excluded pancreatic tumor microenvironment and driving T-cell exhaustion in a sex-dependent manner [3]. Also, Fpr2 -/- mice developed more severe alcohol-associated liver disease with compromised liver regeneration, fewer hepatic monocyte-derived restorative macrophages, and diminished neutrophil oxidative burst capacity [5].

In conclusion, Fpr2 plays essential roles in immune regulation, inflammation, and disease development. Studies using Fpr2 knockout mouse models have significantly enhanced our understanding of its functions in intestinal inflammation, influenza, pancreatic cancer, and alcohol-associated liver disease, highlighting its potential as a therapeutic target in these disease areas.