Ggct (γ-glutamyl cyclotransferase) plays an important role in erythrocyte antioxidant defense and red blood cell survival.

The expression of GGCT (γ-glutamyl cyclotransferase) is upregulated in various human cancers. γ-glutamyl cyclotransferase enzyme activity was originally purified from human red blood cells (RBCs), but the physiological function of GGCT in RBCs is still not clear. Here we reported that Ggct deletion in mice leads to splenomegaly and progressive anaemia phenotypes, due to elevated oxidative damage and the shortened life span of Ggct-/- RBCs. Ggct-/- RBCs have increased reactive oxygen species (ROS), and are more sensitive to H2 O2 -induced damage compared to control RBCs. Glutathione (GSH) and GSH synthesis precursor l-cysteine are decreased in Ggct-/- RBCs. Our study suggests a critical function of Ggct in RBC redox balance and life span maintenance through regulating GSH metabolism.