CA9 and neoplasm: Paradoxically, in hypoxic tumor microenvironment, depletion of NFS1 was shown to display synthetic lethality with suppression of carbonic anhydrase IX (CAIX), likely due to that loss of CAIX activity decreased intracellular pH and increased ROS accumulation, which sensitized hypoxic tumor cells to ferroptosis (Chafe et al., 2021).