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Erythropoietin (EPO) is the central hormone in the regulation of erythropoiesis. Synthesis of EPO and its constitutive release into the circulation are controlled by the transcriptional activity of the EPO gene. A key regulator of EPO is the dimeric hypoxia-inducible transcription factor (HIF), which has three isoforms. Paliege and co-workers provide convincing morphological evidence that it is the HIF-2 isoform that essentially triggers EPO in the kidney, which is the primary source of EPO in the body. [ABSTRACT FROM AUTHOR]