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Indeed, though historically thought to be devoid of organelles, mature RBCs still retain some macromolecular machineries such as ubiquitin transferases and the proteasome 79 , that are critical under physiological conditions (e.g., in response to high-altitude hypoxia to promote the degradation of the adenosine transporter ENT1 80 ) or under pathological conditions to promote protein degradation (e.g., sickle cell disease 81 )