OGFR (opioid growth factor receptor) is a nuclear membrane-associated receptor that binds opioid growth factor (OGF), also known as methionine-enkephalin 1. Unlike classical opioid receptors, OGFR is an integral membrane protein located on the outer nuclear envelope with a unique structure containing imperfect repeats and a bipartite nuclear localization signal 1. The OGF-OGFR complex translocates through nuclear pores to modulate DNA activity and cell proliferation 1. OGFR functions as a tonic inhibitory regulator of cell growth, involved in development, cancer, wound healing, and angiogenesis 1. In disease contexts, OGFR plays complex roles: it contributes to doxorubicin-induced cardiotoxicity by promoting cardiomyocyte apoptosis and ferroptosis through the OGF/OGFR/P21 axis and repression of ferritin genes 2. OGFR is highly expressed in aggressive prostate cancer tissue and is repressed by androgens 3. Therapeutically, OGFR antagonists like naltrexone show promise in treating autoimmune disorders by restoring enkephalin levels 4, accelerating corneal re-epithelialization in diabetic keratopathy 5, and providing cardioprotection against chemotherapy-induced toxicity 2. OGFR represents a unique growth regulatory pathway distinct from classical opioid signaling.