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Complement Component 5a Receptor 1 (C5aR1), also known as CD88, is a high-affinity G protein-coupled receptor (GPCR) essential for mediating potent inflammatory responses. In the tumor microenvironment, C5aR1 activation on myeloid-derived suppressor cells (MDSCs) facilitates immune evasion and metastasis. Crucially, C5aR1 interacts with glycosaminoglycans (GAGs), such as heparin, which act as co-receptors or modulators. These C5aR1-GAG interactions influence ligand recruitment and receptor signaling, making this axis a prime target for developing therapeutic antibodies and small-molecule inhibitors in oncology and autoimmune disorders.