SURF1 encodes a cytochrome c oxidase (COX) assembly factor essential for complex IV biogenesis and stability in the mitochondrial inner membrane 1. As a component of the MITRAC complex, SURF1 regulates the assembly of the electron transport chain's terminal oxidase, which catalyzes oxygen reduction during aerobic respiration 2. SURF1 mutations impair COX activity, reducing it to approximately 32% of normal levels 3, compromising mitochondrial oxidative phosphorylation and cellular energy production. Pathogenic SURF1 variants cause Leigh syndrome, a severe pediatric neurodegenerative disease characterized by symmetric basal ganglia and brainstem lesions, developmental regression, elevated serum lactate, and early mortality (≤50% three-year survival) 4. SURF1 mutations also associate with Charcot-Marie-Tooth disease type 4K and nuclear-encoded complex IV deficiency 1. Over 60 different SURF1 mutations have been identified, with frameshift and nonsense variants causing more severe phenotypes 3. Clinical management includes ketogenic diet and coenzyme Q supplementation, though results remain inconsistent 1. Emerging gene therapy approaches utilizing improved AAV9 vectors show promise for restoring COX activity without cytotoxicity 5. COX activity measurements represent a potential biomarker for disease severity and treatment monitoring 3.