OSER1 (oxidative stress responsive serine rich 1) is an evolutionarily conserved protein that functions primarily in oxidative stress response and longevity regulation. OSER1 is a FOXO-regulated gene 1 that reduces oxidative stress and extends lifespan across multiple species including silkworms, nematodes, and flies 1. The protein actively scavenges hydrogen peroxide both in vitro and in vivo 1, and its overexpression enhances resistance to oxidative stress, starvation, and heat shock 1. Mechanistically, OSER1 maintains mitochondrial functional integrity by preventing fragmentation, sustaining ATP production, and regulating mitochondrial gene expression 1. At the cellular level, OSER1 localizes to the nucleus and exhibits protein-binding capacity involved in cellular responses to hydrogen peroxide 1. Clinically, OSER1 shows relevance as a biomarker in multiple diseases: polymorphic variants associate with human longevity 1, reduced expression correlates with diabetic retinopathy progression 2, and low peripheral blood OSER1-AS1 (a related lncRNA) associates with non-small cell lung cancer severity and poor prognosis 3. Additionally, OSER1-AS1 dysfunction is implicated in rheumatoid arthritis pathology 4 and periodontitis 5. These findings establish OSER1 as a critical mediator of oxidative stress defense and healthy aging with potential diagnostic and therapeutic applications across multiple disease contexts.