Sustained hypoxia appears to be an early and pivotal condition in the pathogenesis of chronic kidney disease, and may induce a number of adaptive/protective or harmful cellular responses. Kojima and colleagues found an upregulation of metallothioneins (MTs) among dozens of altered expression patterns. They demonstrated the astonishing properties of MTs within major intracellular signaling pathways beyond their notorious functions in heavy metal metabolism, detoxification, and ROS scavenging-HRE stimulation during normoxia and hypoxia together with ERK phosphorylation and mTOR activation.