Fine-tuning Formylpeptide Receptor 2 Activation: Signalling Bias and Ligand Binding Mode

Inflammation is a key driver of many cardiometabolic diseases. Formylpeptide receptor 2 (FPR2) is a cell surface protein that can mediate both protective and harmful effects, depending on the compounds that activate it. This thesis investigated how different compounds interact with FPR2 and the signalling pathways they induce. The study identified two distinct clusters of ligands—one associated with beneficial effects and the other with detrimental outcomes in diseased animal models. These clusters activated FPR2 in different ways. The findings provide new insights into FPR2 biology and will help guide the development of targeted therapies for inflammatory cardiometabolic conditions.