Fetuin-A (AHSG), a 59 kDa glycoprotein, consisting of two cystatin-like domains and a smaller unrelated domain, is predominantly synthesized in liver. It is secreted into the blood stream and deposited as a noncollagenous protein in mineralized bones and teeth. Fetuin-A occurs in high serum concentrations during foetal life, whereas its level declines following infection, inflamatory and malignancy. Fetuin-A acts as an important circulating inhibitor of ectopic calcification, frequent complication of many degenerative diseases. Low serum level of Fetuin-A is associated with vascular and valvular calcification, atherosclerosis, malnutrition and higher cardiovascular mortality in chronic renal failure, liver cancer and liver cirrhosis patients on long-term dialysis. AHSG protein represents a natural inhibitor of tyrosinase kinase activity of the insulin receptor. It may play a significant role in regulating postprandial glucose disposal, insulin sensitivity, weight gain, and fat accumulation. The serum and bone-resident Fetuin-A binds to transforming growth factor-β and blocks TGF-β binding to cell surface receptors.