TPI1 (triosephosphate isomerase 1) is a key glycolytic enzyme that catalyzes the reversible conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate, playing essential roles in glucose metabolism and cellular energy production 12. The enzyme functions as a homodimer and its activity can be regulated through post-translational modifications, including phosphorylation at Ser21 by salt-inducible kinases in an LKB1-dependent manner in humans 2. TPI1 also facilitates the production of methylglyoxal, a cytotoxic metabolite that can modify proteins, DNA, and lipids [UniProt]. Beyond its metabolic functions, TPI1 plays crucial roles in cancer progression through multiple mechanisms. It promotes tumor growth by stabilizing oncoproteins like c-Myc through interaction with the AKT-MDM2 pathway, leading to p53 ubiquitination and degradation 3. TPI1 also enhances chemotherapy resistance by promoting autophagy through direct binding to Beclin-1, disrupting Bcl-2-mediated autophagy inhibition 4. In lung regeneration, dopaminylation of TPI1 at glutamine 65 enhances its enzymatic activity, directing metabolic flux toward glucose metabolism and preventing ferroptotic cell death 1. TPI1 deficiency is associated with a rare inherited metabolic disorder affecting red blood cells and causing hemolytic anemia.