Tfrc, also known as transferrin receptor 1, is a crucial protein for iron uptake in cells. It binds to transferrin, which transports iron in the blood, facilitating the entry of iron into cells. This process is integral to maintaining iron homeostasis, a key aspect of numerous cellular functions, including DNA synthesis, energy production, and antioxidant defense. Dysregulation of Tfrc-related iron uptake can disrupt these functions and is associated with various disease processes related to ferroptosis [1-10].

In the context of diseases, knockdown or knockout studies have provided valuable insights. For example, in CVB3 infection, down-regulation of TFRC attenuated ferroptosis, suggesting its role in promoting this form of cell death during the infection [1]. In doxorubicin-induced cardiomyopathy, cardiac-specific Snx3 knockout, which affected TFRC-dependent ferroptosis, significantly alleviated the condition, indicating that SNX3 exacerbates the cardiomyopathy via TFRC-mediated ferroptosis [2]. Inhibition of METTL3, which modifies TFRC mRNA, also ameliorated doxorubicin-induced cardiotoxicity through suppressing TFRC-mediated ferroptosis [3]. In colorectal cancer, knockdown of ANXA10 induced ferroptosis by inhibiting autophagy-mediated TFRC degradation, thereby inhibiting cancer progression [4].

In conclusion, Tfrc is essential for maintaining iron homeostasis and its dysregulation is implicated in multiple disease conditions, particularly those related to ferroptosis. Studies using gene knockout or knockdown models have been instrumental in revealing its role in diseases such as viral infections, cardiomyopathies, and cancer, highlighting its potential as a therapeutic target.