FAHD1 is a mitochondrial metabolic enzyme with dual catalytic functions critical for oxidative metabolism. Structurally, FAHD1 contains a fumarylacetoacetate hydrolase domain and functions primarily as an oxaloacetate tautomerase that converts enol-oxaloacetate to its physiological keto form, preventing succinate dehydrogenase inhibition and maximizing aerobic respiration efficiency 1. FAHD1 additionally acts as an oxaloacetate decarboxylase, catalyzing oxaloacetate conversion to pyruvate and CO₂ as a regulatory enzyme in the TCA cycle 2, and displays acylpyruvase activity on acetylpyruvate and fumarylpyruvate 2. Catalytically, FAHD1's active site features a flexible helical 'lid' that undergoes substrate-driven conformational changes, with key residues (H30, E33, K123) contributing to distinct catalytic mechanisms for both activities 2. FAHD1 depletion impairs mitochondrial electron transport and ATP-coupled respiration, inducing premature cellular senescence via metabolic dysfunction independent of DNA damage 3. Conversely, FAHD1 overexpression reduces reactive oxygen species levels and correlates with aggressive phenotypes in hepatocellular carcinoma, where it drives pyruvate-hyperactive metabolic states and poor prognosis 4. These findings establish FAHD1 as a critical regulator of mitochondrial metabolism with implications in aging and cancer pathogenesis.