TFRC (transferrin receptor) is a cell surface protein primarily responsible for iron ion transport across cellular membranes 1. As a transferrin receptor expressed on the blood-brain barrier and other tissues, TFRC mediates iron uptake by binding transferrin-iron complexes and facilitating their internalization via clathrin-coated pits into endosomal compartments 2. Beyond iron homeostasis, TFRC plays a critical role in ferroptosis—a form of iron-dependent cell death characterized by lipid peroxidation. TFRC upregulation promotes ferroptosis in multiple pathological contexts, including viral infection (CVB3), hepatic ischemia-reperfusion injury, pulmonary fibrosis, psoriasis, temporomandibular joint osteoarthritis, and thrombogenesis 314567. In cancer, YAP-mediated TFRC upregulation enhances ferroptosis sensitivity in mesenchymal cells 8. Clinically, TFRC represents a dual-function target: its cell surface expression enables CNS gene delivery via engineered AAV vectors for treating genetic diseases like Gaucher disease 2, while ferroptosis inhibition through TFRC suppression shows therapeutic potential in inflammatory and degenerative diseases. TFRC dysregulation is associated with Immunodeficiency 46, highlighting its importance in immune function.