However, our investigations reveal that in creg1−/− mutants, decreased TGF‐β/Smad2 signaling could also lead to anemia caused by defective terminal erythroid differentiation and excessive cell apoptosis, implying that TGF‐β/Smad2 signaling may play a protective role in regulating erythropoiesis under in vivo physiological conditions. This evidence concerns the gene SMAD2 and anemia.