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A highly reducing environment is maintained in subcellular compartments, e.g., the cytosol, nucleus, mitochondrial matrix, and peroxisome, to facilitate proper protein folding and activity

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Given that some mutant enzymes retain low-level FAD-binding capacity, a gene + high-dose riboflavin synergy strategy has been proposed: in AIFM1 encephalopathies, low-level AAV transduction re-establishes baseline protein expression, while daily riboflavin doses above 400 mg act as a molecular chaperone to stabilize FAD binding a regimen shown to improve ICARS scores and neuroimaging outcomes (54, 75)