A2M functions as a pan-protease inhibitor produced by the liver, is normally found at high concentrations in the blood, and its expression is inversely correlated with age in humans (Birkenmeier et al., 2003) Recently, A2M purified from blood was approved by the FDA for treating osteoarthritis via direct injection into joints wherein it prevents joint damage by inactivating resident matrix degrading proteases (Wang et al., 2014). Here, A2M is linked to osteoarthritis.