Beyond Glycolysis: Multifaceted Roles of Triosephosphate Isomerase 1 (TPI1) in Malignant Tumor Progression.

Triosephosphate isomerase 1 (TPI1) is a key glycolytic enzyme that catalyzes the reversible interconversion of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. Emerging evidence suggests that TPI1 also participates in cancer-associated non-canonical functions involving altered subcellular localization, protein-protein interactions, signaling regulation, and therapeutic responses. This narrative review summarizes the biochemical properties of TPI1 and critically evaluates its expression patterns, prognostic associations, molecular mechanisms, and therapeutic implications across malignancies. TPI1 is frequently upregulated in several cancer types, although its biological and clinical significance varies substantially among tumors. Experimental studies have identified potential moonlighting functions involving nuclear localization in lung adenocarcinoma and protein-interaction-dependent signaling in breast cancer, glioblastoma, and bladder cancer. In hepatocellular carcinoma, apparently conflicting findings may reflect differences in experimental models, cellular contexts, and intracellular versus extracellular-vesicle-associated TPI1. Emerging evidence also implicates TPI1 in tumor immune regulation and therapeutic resistance, although many findings remain based on computational associations or preclinical models. Current research is limited by insufficient prospective clinical validation and the absence of established, broadly applicable pharmacological strategies targeting TPI1. Collectively, TPI1 represents a context-dependent candidate biomarker and potential therapeutic target in cancer, warranting further mechanistic investigation and clinical validation. REGISTRATION: Not applicable; this article is a narrative review.