While studies in cell culture systems suggest that TFR2 increases EPO sensitivity by enhancing cell surface EPOR and downstream signaling (Forejtnikovà et al., 2010; Fouquet et al., 2021), mice with TFR2 knockout in the bone marrow demonstrate an increase, rather than the predicted decrease, in EPO sensitivity—but only during iron deficiency (Rishi et al., 2016). Here, EPO is linked to nutritional disorder.