Bifunctional enzyme that catalyzes the first two steps in lysine degradation. H2O + L-saccharopine + NADP(+) = 2-oxoglutarate + H(+) + L-lysine + NADPH H2O + L-saccharopine + NAD(+) = (S)-2-amino-6-oxohexanoate + H(+) + L-glutamate + NADH Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 1/6. Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 2/6. Homotetramer. Expressed in all 16 tissues examined with highest expression in the liver. Induced by starvation. The N-terminal and the C-terminal domains contain respectively the lysine ketoglutarate reductase and saccharopine dehydrogenase activity. The disease is caused by variants affecting the gene represented in this entry. In hyperlysinemia 1, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine. Some individuals, however, retain significant amounts of lysine-ketoglutarate reductase and present with saccharopinuria, a metabolic condition with few, if any, clinical manifestations. The protein represented in this entry is involved in disease pathogenesis. A selective decrease in mitochondrial NADP(H) levels due to NADK2 mutations causes a deficiency of NADPH-dependent mitochondrial enzymes, such as DECR1 and AASS. In the N-terminal section; belongs to the AlaDH/PNT family. In the C-terminal section; belongs to the saccharopine dehydrogenase family.