Transferrin

Transferrin, also known as siderophilin, is a glycoprotein circulating in vertebrate blood plasma. It serves as the principal iron transport protein, binding ferric iron (Fe3+) with high affinity and delivering it to cells that express transferrin receptors. Each transferrin molecule contains two iron-binding sites and can shuttle iron safely through the bloodstream, minimizing free iron toxicity.

Most transferrin is produced by the liver as apotransferrin (iron-free); when it binds iron released from intestinal mucosa during absorption or from macrophage recycling, it becomes holotransferrin (holo-Tf). The holo-transferrin binds to transferrin receptor 1 on cell surfaces and is internalized by receptor-mediated endocytosis. Within acidic endosomes, iron is released and transported to cytosolic pools, while apotransferrin dissociates from the receptor and returns to the bloodstream for reuse.

In clinical practice, transferrin levels and iron status are evaluated by measuring serum iron, transferrin concentration, and calculating the total iron-binding capacity (TIBC) or transferrin saturation (TSAT). TSAT equals serum iron divided by TIBC times 100 and indicates how much transferrin binding capacity is occupied by iron; values vary with age and inflammation.

Disorders of transferrin or iron metabolism include iron deficiency, which lowers TSAT; hereditary transferrin deficiency (hypotransferrinemia) is rare and can cause severe anemia, developmental issues, and iron overload in some tissues. Treatment may involve transfusion of plasma products or transferrin supplementation in specific cases.

Transferrin also plays a role in iron delivery to the brain, regulated in part by the transferrin receptor system in the blood-brain barrier, and in fetal and placental iron transport. Uptake of transferrin-iron is mediated primarily by transferrin receptor 1 (TFRC); transferrin receptor 2 (TFR2) contributes to iron sensing and hepcidin regulation in the liver. The protein is a key component of systemic iron homeostasis and a common target in clinical laboratory assessment of iron-related disorders.