alpha-2-Macroglobulin (alpha-2M) is a homotetrameric serum protein consisting of four identical subunits that form dimers through disulfide bonds. Initially, alpha-2M was characterized as a pan-proteinase inhibitor that was able to “bait” proteinases into cleaving specific peptide sequences on alpha-2M. This interaction induces a conformational change in alpha-2M, thus enabling it to “trap” the proteinase and further inhibit its activity. Subsequently, alpha-2M has been shown to function as a carrier protein and regulator of cytokines during inflammation. Circulating transforming growth factor beta (TGF beta) in serum is primarily bound to alpha-2M, which renders TGF∫ inactive. Mutations and deletions in the gene encoding alpha-2M are associated with an increased incidence of Alzheimer's Disease (AD). Alpha-2-macroglobulin-like protein 1 (alpha2ML1) is a related protein that is expressed in the epidermis and may play a role in keratinocyte differentiation.