TRAP1 (TNF receptor associated protein 1) is a mitochondrial HSP90 chaperone that functions as a critical metabolic regulator with ATPase activity 1. TRAP1 negatively regulates mitochondrial respiration and oxidative phosphorylation while promoting aerobic glycolysis 23. The protein maintains mitochondrial homeostasis by interacting with client proteins involved in the electron transport chain and modulating the α-ketoglutarate/succinate ratio 4. TRAP1 plays complex roles in disease pathogenesis, particularly in cancer progression where it sustains various hallmarks including cell death resistance and metabolic reprogramming 5. In vascular smooth muscle cells, TRAP1 promotes senescence and atherosclerosis by increasing lactate production, which drives histone H4K12 lactylation and activates senescence-associated secretory phenotype expression 2. Conversely, in tumor-associated macrophages, TRAP1 downregulation enhances immunosuppressive function and promotes tumor immune evasion through metabolic and epigenetic reprogramming 4. TRAP1 also contributes to chemotherapy resistance in cancer cells by maintaining mitochondrial ATP production and OXPHOS activity 3. Due to its central role in multiple pathologies, TRAP1 has emerged as an attractive therapeutic target, with selective inhibitors being developed to avoid pan-HSP90 toxicity 6.