ME1 (malic enzyme 1) is a cytosolic and mitochondrial oxidoreductase that catalyzes the oxidative decarboxylation of malate to pyruvate in the presence of NADP+, linking glycolysis to the tricarboxylic acid cycle 1. The enzyme generates NADPH, a critical cofactor for reductive biosynthesis and antioxidant defense, with activity comparable to the pentose phosphate pathway and IDH1 in supporting cellular NADPH pools 2. ME1 function is dynamically regulated through phosphorylation and acetylation: PGAM5-mediated dephosphorylation at S336 combined with ACAT1-mediated acetylation at K337 promotes ME1 dimerization and activation, enhancing lipogenesis and NADPH production in colorectal cancer 3. Similarly, ERK2 phosphorylation at T103 stabilizes ME1 against proteasomal degradation, promoting lipid metabolism and suppressing reactive oxygen species 4. ME1 upregulation occurs in multiple malignancies, particularly colorectal and pancreatic cancers, where it supports the enhanced lipogenic metabolism characteristic of tumor cells. Clinically, ME1 inhibition in pulmonary hypertension promotes protective adenosine signaling in endothelial cells through regulating the malate-aspartate NADH shuttle, improving vascular function and reducing disease progression 1. These findings establish ME1 as a metabolic hub integrating energy production, lipid synthesis, and redox homeostasis in both normal physiology and disease pathogenesis.