OXR1 (oxidation resistance 1) is a highly conserved gene encoding a protein that protects cells from oxidative damage through multiple mechanisms 1. The primary function involves maintaining mitochondrial DNA integrity and counteracting hydrogen peroxide-induced oxidative stress by regulating antioxidant pathways involving p21, leading to upregulation of antioxidant genes GPX2 and HO-1 1. OXR1 localizes to both mitochondria and nucleus, and is induced by heat and oxidative stress 2. Mechanistically, OXR1 regulates V-ATPase activity at the Golgi apparatus and trans-Golgi network through direct binding to its catalytic subunit, maintaining optimal pH for protein glycosylation 3. Additionally, OXR1 maintains retromer function, which is critical for proper protein trafficking and preventing endolysosomal defects 4. OXR1 also influences histone arginine methylation by activating protein arginine methyltransferases during neurodevelopment 5. Disease-wise, loss-of-function mutations cause cerebellar atrophy, early-onset epilepsy, developmental delay, and cognitive disabilities 5. Clinically, OXR1 expression declines with age and is associated with neurological diseases, making it a potential therapeutic target for neurodegeneration and age-related disorders 4.