Alpha-2-HS glycoprotein (AHSG), also known as fetuin-A, is a protein produced by the liver and secreted into the bloodstream. It belongs to the group of binding proteins that mediate the transport and utilization of various substances in the blood. Knockout mouse experiments have shown that fetuin-A is a potential systemic inhibitor of calcification. It plays an important role in countering insulin resistance induced by free fatty acids in the liver. In prediabetes, fetuin-A can predict adverse blood sugar outcomes. It is also associated with increased risk of non-alcoholic fatty liver disease and cardiovascular diseases. During sepsis and endotoxemia, fetuin-A acts as a negative acute-phase reactant, promoting wound healing and exerting neuroprotective effects in Alzheimer’s disease. Decreased levels of fetuin-A are associated with increased risk of exacerbation in obstructive lung diseases, Crohn’s disease, and ulcerative colitis.