ROMO1 (reactive oxygen species modulator 1) is a redox-sensitive mitochondrial inner membrane protein that plays multifaceted roles in cellular homeostasis and disease pathogenesis. Functionally, ROMO1 regulates mitochondrial reactive oxygen species (ROS) production and protects the mitochondrial cysteinome from oxidative damage 1. ROMO1 overexpression preserves mitochondrial thiol pools, promotes energy metabolism, and maintains calcium uniport while inhibiting membrane permeability transition 1, demonstrating protective effects against age-related mitochondrial decline. In disease contexts, ROMO1's roles are complex and context-dependent. ROMO1 is frequently overexpressed in multiple cancers including glioblastoma, where it drives ROS production and cellular proliferation through cell cycle arrest evasion 2. Similarly, in HPV-associated cancers, ROMO1 mediates mitochondrial reprogramming and metabolic shifts toward glycolysis 3, and in castration-resistant prostate cancer, ROMO1 upregulation via PKLR/MYCN signaling promotes neuroendocrine differentiation 4. Conversely, ROMO1 contributes to pathological ROS signaling in inflammatory diseases. In COPD, ROMO1-mediated mitochondrial ROS activates STAT6 phosphorylation, driving airway mucus hypersecretion 5. ROMO1 emerges as a shared genetic component across autoimmune diseases (rheumatoid arthritis, multiple sclerosis, type 1 diabetes), regulating monocyte function via ROS pathways 6. Therapeutically, ROMO1 represents a potential target: blocking ROMO1-mediated ROS production enhances drug-induced apoptosis in ovarian cancer 7, while ROMO1 inhibition shows promise in multiple cancer and inflammatory disease models.