NDUFS6 encodes an accessory subunit of mitochondrial respiratory complex I (CI) that plays a critical role in electron transfer from NADH to ubiquinone within the electron transport chain 1. As a 13 kiloDalton protein localized to the iron-sulfur fraction of CI's peripheral arm, NDUFS6 is essential for proper CI assembly and oxidative phosphorylation 1. While not directly involved in catalysis, NDUFS6 is indispensable for complex I function and cellular energy metabolism 2. Loss of NDUFS6 function causes mitochondrial complex I deficiency, leading to severe mitochondrial diseases including Leigh syndrome and mitochondrial cardiomyopathy characterized by reduced ATP synthesis and increased reactive oxygen species accumulation 123. NDUFS6 mutations have been identified in neonatal lactic acidemia, peripheral neuropathies, and cardiomyopathy patients 45. Beyond disease, NDUFS6 regulates adult stem cell aging through mitochondrial ROS control 6, and selective NDUFS6 inhibition enhances anti-tumor immunity by promoting MHC-I antigen presentation in cancer cells 78. These findings underscore NDUFS6's dual roles in cellular bioenergetics and as a potential therapeutic target.