ETFDH (electron transfer flavoprotein dehydrogenase) is a mitochondrial enzyme that accepts electrons from electron transfer flavoprotein (ETF) and transfers them to ubiquinone, serving as a critical link in the electron transport chain. 1 This oxidoreductase activity is essential for fatty acid β-oxidation and energy metabolism, enabling the mobilization of stored triglycerides during metabolic demands. 2 Mechanistically, ETFDH operates at the mitochondrial inner membrane through its flavin adenine dinucleotide (FAD) and iron-sulfur cluster cofactors, facilitating electron transfer from acyl-CoA dehydrogenases to the ubiquinone pool. 1 Loss of ETFDH function impairs this critical metabolic checkpoint, triggering lipid accumulation and enhanced oxidative stress. Pathogenic ETFDH mutations cause Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), also termed Glutaric Aciduria Type II (GA2), an autosomal recessive metabolic disorder with neonatal and late-onset presentations. 3 4 Clinical manifestations include muscle weakness, metabolic acidosis, and notably, polycystic kidney disease in early-onset cases. 1 ETFDH variants represent a significant genetic cause of metabolic myopathy and hyperCKemia. 5 Clinically, patients with ETFDH-deficiency respond to supplementation with riboflavin (vitamin B2), L-carnitine, and coenzyme Q10, providing symptomatic relief by supporting residual metabolic function. 3