Mouse Erythropoietin (EPO) was initially cloned from mouse genomic libraries using human and monkey cDNA probes. Mouse and human EPO are 80% identical at amino acid and nucleotide levels. EPO is a glycoprotein composed of 40-60% carbohydrates, and its molecular weight varies from 30-34 kD depending on the carbohydrate percentage. Hypoxia induces erythropoiesis, and hypoxia inducible factor (HIF) is directly involved in EPO expression. HIF is a heterodimer (HIF-1alpha, HIF-2alpha, and beta subunits) transcription factor, and it is regulated by HIF-prolyl hydroxylase (HIF-PH) that hydroxylates the alpha subunits, targeting them for ubiquitination and subsequent degradation. HIF-PH is a sensor of levels of iron, oxygen, and metabolic activity. High levels of HIF protein induce EPO production in the kidney and liver, and mobilization of iron to support erythropoiesis. EPO binds to the EPOR, and transcripts of this receptor have been detected in non-erythroid precursors such as endothelial cells and renal proximal epithelial cells; nevertheless, it has been published that functional erythropoietin receptor is not detected in endothelial, cardiac, neuronal, and renal cells. Several transcriptions factors play a role in the expression of EPOR such as GATA 1, Friend of GATA (Fog1), and the erythroid specific factor SCL/Tal 1. EPO has been used in the treatment of anemia associated with chronic kidney disease, cancer patients on chemotherapy, and antiviral HIV therapy.