AASS (aminoadipate-semialdehyde synthase) is a bifunctional mitochondrial enzyme catalyzing the first two steps of lysine catabolism through its saccharopine dehydrogenase activities 1. The enzyme converts lysine to α-aminoadipic semialdehyde, a critical early step in the lysine degradation pathway. AASS also localizes to the nucleus and cytosol with reported transcriptional corepressor activity and histone binding capacity, suggesting additional regulatory functions beyond lysine metabolism. Clinically, AASS mutations cause hyperlysinemia type 1, characterized by elevated plasma lysine levels. Additionally, AASS dysfunction is implicated in glutaric aciduria type I (GA1), an inherited metabolic disorder where defective glutaryl-CoA dehydrogenase downstream causes accumulation of neurotoxic metabolites in the central nervous system 1. The lysine degradation pathway integrity, which depends on AASS function, is therefore essential for preventing toxic metabolite buildup. Therapeutically, AASS inhibition via substrate reduction therapy shows promise in GA1 models 1. AAV9-delivered microRNA targeting AASS reduced neurotoxic metabolite accumulation in the striatum, prevented neuropathological changes, and improved survival in GA1 mouse models, supporting AASS inhibition as a potential gene therapy strategy for this severe inherited metabolic disorder.