ALDH7A1 (aldehyde dehydrogenase 7 family member A1) encodes α-aminoadipic semialdehyde dehydrogenase, a key enzyme in lysine oxidation 1. The protein functions as a critical ferroptosis suppressor through dual mechanisms: it generates membrane NADH to support FSP1 activity and directly reduces lipid peroxidation by consuming reactive aldehydes like 4-hydroxynonenal 2. Upon ferroptotic stress, AMPK-mediated phosphorylation recruits ALDH7A1 to plasma membranes, stabilizing FSP1 and enhancing antioxidant defense 2. Additionally, ALDH7A1 regulates cellular energy homeostasis during metabolic stress by inhibiting COPI-mediated transport. Pathogenic ALDH7A1 mutations cause pyridoxine-dependent epilepsy (PDE-ALDH7A1), an autosomal recessive developmental and epileptic encephalopathy with estimated incidence of 1:64,352 live births 3. This disorder results from impaired lysine metabolism, causing accumulation of toxic metabolites that inactivate pyridoxal 5'-phosphate (PLP), an essential cofactor for neurotransmitter synthesis 4. While pharmacologic pyridoxine achieves seizure control, most patients experience developmental delay and intellectual disability without adjunctive lysine-restriction therapy and arginine supplementation 1. The heterogeneous phenotypic spectrum includes brain malformations, refractory seizures, and multisystem neonatal manifestations 5. Early diagnosis through genetic testing is critical for optimizing cognitive outcomes. Rare disease experts strongly support ALDH7A1 inclusion in newborn screening programs 6.