<p>Haptoglobin is a plasma protein that binds haemoglobin. The resulting complex is too large to be excreted by the kidney, thereby preventing loss of iron and damage to the kidney. The haptoglobin-haemoglobin complex is degraded in the liver, which is also the site of haptoglobin synthesis. The mature haptoglobin molecule is a tetramer, consisting of two alpha and two beta chains. Alpha and beta chains arise from proteolytic processing of the same precursor. Each beta chain can bind an alpha-beta heterodimer of haemoglobin so that each haptoglobin tetramer binds one haemoglobin tetramer. In <taxon tax_id="9598">Pan troglodytes</taxon> (Chimpanzee), haptoglobin genes form a small multigene family of three genes: HP, HPR (haptoglobin-related protein, which may be non-functional), and HPP (haptoglobin-primate) [<cite idref="PUB00011145"/>]. In contrast, most humans have a two-gene cluster due to an unequal homologous crossover event between HPR and HPP in the human lineage [<cite idref="PUB00011146"/>]. Such events may be common among these closely related genes as <taxon tax_id="9544">Macaca mulatta</taxon> (Rhesus macaque) was found to have haplotypes of one- or two-gene clusters that appear to have formed from unequal crossover among an ancestral three-gene cluster [<cite idref="PUB00011147"/>]. The haptoglobin precursor contains a signal sequence, a sushi domain (in mature alpha chain), and a trypsin domain (in mature beta chain) which belongs to the MEROPS peptidase family S1 (clan PA(S)). Haptoglobins have no enzymatic activity as the active site residues typical of trypsin-related proteases are not conserved, they are therefore classed as non-peptidase homologues. A common allelic variant in humans contains two sushi domains.</p>