Strikingly, EpoR-HM mice arerestricted to the binary signaling mode, which rescues these mice from fatalperinatal anemia by promoting binary survival decisions in erythroblasts.However, the absence of the graded p-Stat5 response in the EpoR-HM mice preventsthem from accelerating red cell production in response to stress, including afailure to upregulate the transferrin receptor, which we show is a novel stresstarget. Here, STAT5B is linked to anemia.