Transferrin receptor protein 1 and 2 (TfR1/2)

Transferrin receptor 1 (TfR1) and Transferrin receptor 2 (TfR2) are critical transmembrane glycoproteins involved in cellular iron uptake and systemic iron homeostasis [1, 6]. TfR1 is ubiquitously expressed and facilitates the internalization of iron-bound transferrin through receptor-mediated endocytosis, a process essential for cell growth and proliferation [5, 11]. Due to its high expression on malignant cells and the blood-brain barrier (BBB) endothelium, TfR1 is a major target for cancer therapy and as a "molecular shuttle" for delivering drugs to the central nervous system [14, 20]. TfR2, primarily expressed in the liver and erythroid cells, serves as a sensor of circulating iron levels and regulates the production of hepcidin, the master regulator of iron balance [4, 10]. Therapeutic strategies targeting these receptors include antibody-drug conjugates for oncology and bispecific antibodies designed to cross the BBB via transcytosis [7, 19]. However, targeting these receptors requires careful management of potential side effects, such as anemia and the disruption of systemic iron regulation [14, 20].

Other names

CD71TFRCTFR2HFE3T9p90TRTransferrin receptor 1Transferrin receptor 2

Drugs targeting Transferrin receptor 1 and 2 primarily utilize receptor-mediated endocytosis for intracellular delivery of therapeutic agents or receptor-mediated transcytosis to facilitate the passage of large molecules across the blood-brain barrier [1, 14, 20]. In oncology, targeting TfR1 can inhibit iron-dependent cell proliferation or deliver cytotoxic payloads directly to tumor cells [11, 13]. Modulating TfR2 is used to regulate systemic iron levels by influencing hepcidin expression, which is vital for managing iron overload disorders like hereditary hemochromatosis [4, 10].