Chemerin is a novel protein identified as the natural ligand of ChemR23 (chemerinR), a previously orphan G protein-coupled receptor expressed in immature dendritic cells and macrophages. It is a member of the Cystatin superfamily. Chemerin is synthesized as a 163 aa secreted precursor, prochemerin, which contains a hydrophobic 20 aa N-terminal sequence, an intervening 137 aa Cystatin fold-containing domain, and a six aa C-terminal prosegment. It is activated by proteases of the coagulation, fibrinolytic, and inflammatory cascades and converted into a full agonist of chemerinR by proteolytic removal of the last six amino acids.Chemerin is a chemoattractant for cells bearing the Chem R23 receptor, including plasmacytoid dendritic cells and tissue macrophages.