Epo (Erythropoietin) is the primary regulator of erythropoiesis and is critical for tissue oxygenation under both steady-state conditions and after acute blood loss or hypoxia. The EPO R is the primary receptor that binds to and transmits the activation signal of the EPO cytokine.ERO R is a member of the type I cytokine receptor superfamily. It usually exists as a homodimer and expressed extensively in EPO-responsive BM erythroid progenitors (BFU-E and CFU-E). The interaction of EPO with EPO R at the level of proerythroid cells activates proliferation, increases survival and promotes cell-restricted lineage erythroid differentiation. EPO also binds to the heterodimeric complex EPO-R on non-erythroid tissues (brain, heart, retina, kidney and others). This heterodimeric complex consists of one chain of EPO-R and a ubiquitous colony-stimulating factor 2 receptor β-chain (CD131). This heterodimeric receptor has been called the tissue protective receptor (TPR) of EPO. Although the interaction of EPO with TPR does not initiate erythropoiesis, it signals biochemical cascades (activation of PI3K, MARK, STAT5 and others), leading to the protection of cells from apoptosis, degeneration and cytotoxicity in general.