What it is
Erythropoietin is a hormone made mainly by the kidney. UniProt's record (P01588) gives a 193-residue precursor: a 27-residue signal sequence that steers it out of the cell, then a 166-amino-acid chain. That chain carries three N-linked sugar chains and one O-linked one, and is held by two disulfide bonds.
At 166 residues, erythropoietin is a protein, about four times the 40-residue line US regulation uses to separate peptides from proteins (21 CFR 600.3). The peptide-versus-protein entry explains where that line falls. The library carries it for two reasons: people arrive with the name from a prescription or a blood test, and a short peptide on the market, ARA-290, was built from one of its surfaces.
The 1985 paper that cloned the human gene (Jacobs et al., Nature, PMID 3838366) describes it as a glycoprotein that "regulates the level of oxygen in the blood by modulating the number of circulating erythrocytes", produced in the kidney or liver of adults and the liver of the fetus. The same paper pointed to the use the cloning opened up: anaemia, "particularly in chronic renal failure".
What it does
UniProt's function annotation is short: erythropoietin regulates the production and maturation of red blood cells and keeps the circulating red-cell mass at a physiological level. It does this by binding its receptor (EPOR) on red-cell precursors in the bone marrow, which pairs the receptors and switches on the JAK2 signalling enzyme.
The trigger is oxygen. When oxygen delivery falls, the kidney makes more erythropoietin; when it is restored, production drops. The way cells sense oxygen and switch genes such as this one on was the subject of the 2019 Nobel Prize in Physiology or Medicine, awarded to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza "for their discoveries of how cells sense and adapt to oxygen availability" (nobelprize.org).
| What is described | How firm |
|---|---|
| Sets red-cell production in response to oxygen | Human physiology; UniProt annotation and the 1985 cloning paper |
| Made mainly in the adult kidney | Stated in the 1985 cloning paper |
| Recombinant versions reduce transfusions in approved anaemias | FDA-approved labels |
| Pushing haemoglobin higher is safe | Contradicted by controlled trials — see the boxed warning below |
The medicines, and their warning
Cloning the gene let companies make erythropoietin in cell culture. FDA application data read on 2026-10-27 list four approved US versions, all prescription-only:
| Medicine | Application | Approved |
|---|---|---|
| Epogen / Procrit (epoetin alfa) | BLA103234, Amgen | 1989-06-01 |
| Aranesp (darbepoetin alfa) | BLA103951, Amgen | 2001-09-17 |
| Mircera (methoxy polyethylene glycol-epoetin beta) | BLA125164, Hoffmann-La Roche | 2007-11-14 |
| Retacrit (epoetin alfa-epbx, a biosimilar) | BLA125545, Hospira | 2018-05-15 |
The labels group them as erythropoiesis-stimulating agents (ESAs), and every label read for this entry opens with the same boxed warning: ESAs increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access and tumour progression or recurrence. The Epogen label (effective 2026-06-23) states that in controlled trials in chronic kidney disease, patients given ESAs to target a haemoglobin above 11 g/dL had greater risks of death, serious cardiovascular reactions and stroke, and that "no trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks." For cancer, it states that ESAs shortened overall survival or increased tumour progression or recurrence in clinical studies.
That warning is the most useful single fact about the medicines: the hormone that makes red blood cells is not a case where more is better. This entry reports what the labels say; decisions about these drugs belong to the prescribing clinician.
The blood test
Many readers meet erythropoietin as a number. MedlinePlus's encyclopedia page on the EPO test (review date 2025-07-09) gives a normal range of 2.6 to 18.5 milliunits per millilitre (mU/mL), and says ranges vary slightly between laboratories.
The page lists what it associates with each direction:
| Result | What MedlinePlus lists |
|---|---|
| Higher than normal | Low blood oxygen, including at high altitude; rarely, a tumour that releases EPO |
| Lower than normal | Chronic kidney disease, anaemia of chronic disease, polycythemia vera |
A raised value in someone who is anaemic is the body responding as expected — the page notes that people with too few red cells produce more EPO. What a reading means for any one person is for the clinician who ordered it. This entry reports the source's ranges and lists; it does not interpret results.
The peptide that came from it
ARA-290, also called cibinetide, is a short synthetic peptide derived from a region of erythropoietin that does not drive red-cell production. It was developed to keep a tissue-protective signal while dropping the blood-forming one. It is not an approved medicine; its small trial record, including one placebo-controlled phase 2 with posted results, is set out in its own entry.
Where it stands
- The hormone: made by the body, chiefly the kidney; a glycoprotein in the EPO/TPO family (UniProt).
- The medicines: four approved US versions, the first in 1989, all under the same boxed warning.
- Published record: PubMed returns 35,843 records for erythropoietin, 1,739 tagged as randomised controlled trials; ClinicalTrials.gov lists 1,335 studies that mention it (all 2026-10-27).
- Not covered here: its use in sport, which is a doping subject rather than a compound question; this entry gives no figures for it.
Related reading
Hepcidin is the hormone on the iron side of red-cell production: erythropoietin sets how many cells are made, hepcidin how much iron reaches them. Somatropin and prolactin are the library's other entries on hormones large enough to count as proteins.