C5AR2 (C5a Receptor 2), also known as C5L2 or GPR77. is a G protein-coupled receptor (GPCR) that binds complement-derived anaphylatoxins C5a and C5a des-Arg. Initially considered a "decoy receptor" due to its lack of classic signaling activity, recent studies suggest it plays regulatory roles in modulating inflammatory responses. Unlike its homolog C5AR1 (C5aR1), C5AR2 does not couple to G proteins but may signal through β-arrestin-dependent pathways, influencing immune cell migration, cytokine release, and metabolic processes. It is expressed in immune cells (neutrophils, macrophages), adipocytes, and various tissues, implicating it in diseases like sepsis, asthma, metabolic disorders, and cancer. C5AR2 antibodies are critical tools for studying its function, localization, and ligand interactions. They help elucidate its dual role in pro- and anti-inflammatory processes, particularly in balancing complement activation. Therapeutic interest in C5AR2-targeting antibodies is growing, with potential applications in inflammatory diseases and immune modulation. However, its complex biology, including tissue-specific effects and crosstalk with C5AR1. necessitates further research to clarify its mechanistic contributions and therapeutic potential.