NDUFC2 encodes an accessory subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase) that is essential for proper assembly rather than catalytic activity 1. The protein plays a crucial role in Complex I biogenesis, particularly in assembling the membrane arm and ND2 module of the holoenzyme 1. NDUFC2 deficiency severely impairs mitochondrial function by reducing Complex I assembly and activity, decreasing mitochondrial membrane potential and ATP levels, while increasing reactive oxygen species production 23. This mitochondrial dysfunction has significant disease implications. Bi-allelic pathogenic variants in NDUFC2 cause early-onset Leigh syndrome with stalled Complex I biogenesis 1. The common rs11237379 polymorphism, where the T allele reduces gene expression, associates with increased susceptibility to early-onset ischemic stroke 2, cardiac hypertrophy in hypertensive patients 4, and acute coronary syndrome recurrence 5. NDUFC2 deficiency also exacerbates endothelial-mesenchymal transformation during ischemia-reperfusion through NLRP3 activation 6 and impairs autophagy, contributing to stroke development in hypertensive models 7. These findings establish NDUFC2 as a critical mitochondrial gene whose deficiency predisposes to cardiovascular and neurological diseases through Complex I dysfunction.