ME3 (malic enzyme 3) is a mitochondrial enzyme that catalyzes the oxidative decarboxylation of (S)-malate to pyruvate using NADP+ as a cofactor, with the reverse reaction occurring at significantly lower efficiency 1. The enzyme localizes to the mitochondrial matrix and plays a key role in cellular metabolism by participating in malate metabolic processes and pyruvate biosynthesis. Genetic variants in the ME3 locus have been identified as risk factors for primary open-angle glaucoma (POAG) through genome-wide association studies 2. Clinical studies demonstrate that patients with higher ME3 genetic risk scores show increased prevalence of paracentral visual field loss, a specific glaucoma phenotype, with larger SNP effect sizes correlating with lower ME3 expression levels 2. This suggests that reduced ME3 function may contribute to glaucoma pathogenesis, potentially through compromised mitochondrial metabolism in retinal cells. The association between ME3 genetic variants and specific glaucoma phenotypes indicates clinical significance for risk stratification and personalized management of POAG patients, though functional studies are needed to fully understand how these variants impact mitochondrial function in glaucoma pathogenesis.