Transferrin receptor 1 (TfR1) (TfR1)

Transferrin receptor 1 (TfR1), also known as CD71, is a transmembrane glycoprotein that plays a central role in cellular iron homeostasis by mediating the uptake of transferrin-bound iron (UniProt P02786). It is highly expressed on reticulocytes, which are immature red blood cells, to satisfy the high iron demand required for hemoglobin synthesis during the final stages of erythropoiesis (StatPearls, 2023). Beyond iron transport, TfR1 has been identified as the essential receptor used by the Plasmodium vivax parasite to recognize and invade reticulocytes, a key step in the malaria lifecycle (Gruszczyk et al., Science, 2018). Because TfR1 is significantly upregulated in many cancers to support rapid cell division, it is a frequent target for monoclonal antibodies and antibody-drug conjugates like praluzatamab ravtansine (PubMed, 2021). Additionally, its ability to undergo endocytosis makes it an attractive vehicle for delivering therapeutics across the blood-brain barrier (PubMed, 2020). Safety considerations for drugs targeting TfR1 include potential disruption of systemic iron balance and toxicities related to its expression in the bone marrow and other proliferative tissues (Journal of Clinical Investigation, 2021).

Other names

CD71TFRCTFR1Transferrin receptor protein 1p90T9

Mediates cellular iron uptake by binding to ferric-transferrin complexes and internalizing them via clathrin-mediated endocytosis; also acts as a primary entry receptor for Plasmodium vivax by binding the parasite protein PvRBP2b (Gruszczyk et al., Science, 2018).