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Maintaining oxygen homeostasis is of vital importance for the survival and development of mammalian cells. Hypoxia (below-normal levels of oxygen in air, blood and tissue) can potentially lead to cellular dysfunction and ultimately cell death and is a feature of many pathological conditions. Understanding how reduced oxygen levels may contribute to or even promote disease is a significant facet of developing new therapeutic options. A recent study by Cramer et al. gives a fresh insight into these mechanisms and raises questions over whether hypoxia is more than just a regulator of angiogenesis [1].