?-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 thatwas 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 inhibit its further activity. Subsequently, ?-2M has also been shown to function as a carrier protein and regulator of cytokines during inflammation. Circulating transforming growth factor ? (TGF?) in serumis primarily bound to ?-2M,which renders TGF? inactive. ?-2M also binds to IL-6 and, thereby, increasesthe concentration of IL-6 near lymphocytes, hepatocytes and stem cells involved inmediating the inflammatory cascade. Mutations and deletions in the gene encoding ?-2M are associated with an increased incidence of Alzheimer’s Disease (AD),which isconsistent with the role of ?-2M inmediating the clearance and degradation of A?, the major component of ?-Amyloid deposits accumulated during AD.