HIF1α transcriptionally activates NOX4 in response to hypoxia in vascular cells,20 whereas in renal cell carcinoma NOX4 may help maintain HIF2α expression.101 However, NOX4 can also regulate HIF protein levels through the inhibition of prolyl hydroxylase-2 (PHD2, which regulates HIF stability). Here, NOX4 is linked to hereditary clear cell renal cell carcinoma.