?-2-Macroglobulin (?-2M) is a homotetrameric serum protein consisting of four identical subunits that form dimers through disulfide bonds. Initially, ?-2M was characterized as a pan-proteinase inhibitor that was able to "bait" proteinases into cleaving specific peptide sequences on ?-2M. This interaction induces a conformational change in ?-2M, thus enabling it to "trap" the proteinase and further inhibit its activity. Subsequently, ?-2M has been shown to function as a carrier protein and regulator of cytokines during inflammation. Circulating transforming growth factor ? (TGF?) in serum is primarily bound to ?-2M, which renders TGF? inactive. ?-2M also binds to IL-6 and, thereby, increases the concentration of IL-6 near lymphocytes, hepatocytes and stem cells involved in mediating the inflammatory cascade. Mutations and deletions in the gene encoding ?-2M are associated with an increased incidence of Alzheimer's Disease (AD), which is consistent with the role of ?-2M in mediating the clearance and degradation of A ?, the major component of ?-Amyloid deposits accumulated during AD.