β2-Glycoprotein I: evolution, structure and function

beta(2)-Glycoprotein I (beta(2)-GPI) is a protein that circulates in blood at high concentrations. The function of beta(2)-GPI has long been an enigma. More than 20 years ago, it was discovered that beta(2)-GPI is the major antigen for the circulating antibodies in the antiphospholipid syndrome. However, this knowledge has not advanced our understanding of the physiologic role of the protein. In recent years, new insights have suggested an important function of this protein in innate immunity. beta(2)-GPI was found to scavenge lipopolysaccharide and was able to clear unwanted anionic cellular remnants such as microparticles from the circulation. The function of beta(2)-GPI seems to depend on the structural conformation of the protein, and it has been established that beta(2)-GPI can exist in at least two conformations. In this review, we will highlight and summarize the current knowledge on this protein.