Fetuin (also designated a-2-z-globulin or a-2-HS-glycoprotein) is a secreted plasma protein that is expressed in hepatocytes, monocyte/ macrophages and in bone and is down-regulated during injury and inflammation. Fetuin preferentially binds to and carries calcium and barium ions in the blood, where it is thought to mediate serum calcium homeostasis and mineralization, and to potentially participate in the transport of bioactive molecules. Additionally, fetuin has been shown to function as an acute phase anti-inflammatory mediator that is critical to regulating the innate immune response following tissue injury. During inflammation, circulating fetuin levels substantially decrease as fetuin becomes associated with the membranes of macrophages. This membrane associated form of fetuin acts as an opsonic participant by potentiating the entry of cationic small molecules into the activated macrophage, which in turn facilitates macrophage-deactivating mechanisms.