FetuinA

Fetuin-A, also known as alpha-2-HS-glycoprotein, is a secreted glycoprotein encoded by the AHSG gene in humans. It is produced predominantly by hepatocytes and circulates at relatively high levels in adult plasma and fetal serum. The protein is heavily glycosylated and has a molecular weight of about 60–63 kDa.

The primary physiological role of fetuin-A is to inhibit ectopic mineralization. It binds calcium and phosphate and forms calciprotein particles that help stabilize minerals in the circulation and prevent spontaneous precipitation in soft tissues and the vasculature. In experimental models, absence of fetuin-A leads to widespread soft tissue calcification and related pathology, illustrating its protective function against pathological mineral deposition.

In addition to mineralization control, fetuin-A acts as a hepatokine involved in metabolic regulation and inflammation. It can influence insulin signaling in some tissues and, in the presence of saturated fatty acids, can participate in Toll-like receptor 4–mediated inflammatory pathways. Clinically, higher fetuin-A levels have been associated with insulin resistance and metabolic syndrome, while lower levels have been linked to reduced calcification risk in certain conditions. In chronic kidney disease, reduced fetuin-A levels are associated with vascular calcification and higher mortality risk, underscoring its role in protecting against ectopic mineral deposition.

Clinical and research relevance: Fetuin-A is studied as a biomarker of calcification risk and metabolic disease and is considered a potential therapeutic target to prevent pathological calcification. The AHSG gene is conserved across mammals, reflecting its evolutionary significance.