ETFA (electron transfer flavoprotein subunit alpha) is a mitochondrial matrix protein that functions as a key hub in cellular energy metabolism. As a subunit of the heterodimeric electron transfer flavoprotein complex, ETFA accepts electrons from multiple mitochondrial dehydrogenases involved in fatty acid and amino acid catabolism, including acyl-CoA dehydrogenases and glutaryl-CoA dehydrogenase 1. These electrons are subsequently transferred to the mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase, enabling completion of fatty acid β-oxidation and amino acid metabolism 1. Beyond canonical metabolic roles, ETFA participates in emerging cellular processes: it facilitates ferroptosis (oxidative cell death) through fatty acid β-oxidation-dependent mitochondrial reactive oxygen species production 2, and its stabilization by hepatocyte immunoglobulin κ promotes hepatocellular carcinoma progression through enhanced lipid metabolism 3. Pathologically, ETFA deficiency causes glutaric aciduria type 2A, an inherited metabolic disorder characterized by severe hypoketotic hypoglycemia and acidosis 4. Recently, genetic studies identified elevated ETFA expression as associated with increased schizophrenia risk 5, while paradoxically, ETFA variants show protective effects against dilated cardiomyopathy 6. ETFA also responds to riboflavin supplementation in multiple acyl-CoA dehydrogenase deficiency 1, suggesting therapeutic potential through metabolic cofactor modulation.