Innate repair receptor (IRR)

The innate repair receptor is a heteromeric cell surface complex formed by the association of the erythropoietin receptor subunit with the β-common chain (CD131), a member of the type I cytokine receptor family. Unlike the homodimeric erythropoietin receptor that mediates red blood cell production, this heteromer is upregulated locally at sites of tissue injury or metabolic stress. Its activation—by endogenous ligands such as hyposialated EPO or synthetic peptides like ARA290—triggers anti-inflammatory, anti-apoptotic, and regenerative pathways while avoiding hematopoiesis. The innate repair receptor has been implicated as a therapeutic target for conditions involving nerve damage (neuropathies), acute kidney injury, diabetes complications, and inflammatory diseases. Selective agonists are being developed to harness its protective functions without increasing risks associated with high-dose erythropoietin therapy.

Other names

EPOR/βcREPO receptor/β-common receptor heteromerErythropoietin receptor–β-common (CD131) heteromerEPOR/bcR

Activation of anti-inflammatory and tissue-protective pathways via IRR agonism. Selective activation by nonerythropoietic peptides like ARA290 or pHBSP triggers pro-regenerative signaling without stimulating erythropoiesis. Engagement of PI3K/Akt, STAT3, and MAPK signaling cascades for cytoprotection and tissue healing.