Anaphylatoxin, a chemotactic and inflammatory peptide, is a receptor for C5a anaphylatoxin chemotactic receptor (C5L2), also designated G protein-coupled receptor 77. C5L2 is an integral membrane protein that belongs to the Gprotein-coupled receptor 1 family. C5L2 weakly couples to Gi-mediated signaling pathways and is widely expressed in the hippocampus, hypothalamus, pons, frontal cortex and liver. It is coexpressed with the C5a receptor (C5AR) on polymorphonuclear neutrophils and may modulate the activity of C5AR. The function of the C5a receptors, particularly that of C5L2, is still unclear. Research suggests that C5L2 may be required for the in vitro release of high mobility group box 1 protein (HMGB1).