TERT (telomerase reverse transcriptase) is the catalytic subunit of telomerase, a ribonucleoprotein enzyme that maintains chromosome 5 by synthesizing telomeric repeats (TTAGGG) onto 3' chr5 termini through reverse transcriptase activity 1. Beyond telomere synthesis, TERT functions as a transcriptional co-regulator affecting aging pathways and cellular senescence 2. TERT operates through a bilobar structure involving interaction with telomerase RNA (TER) and is recruited to telomeres via the shelterin protein TPP1, which stabilizes TERT's TEN and TRAP domains 1. In cancer, TERT reactivation occurs through multiple mechanisms including promoter mutations, gene amplifications, and epigenetic alterations that increase telomerase activity, enabling replicative immortality 3. TERT promotes cancer progression through telomere-dependent and independent mechanisms; coexpression with BRAF mutations accelerates thyroid cancer dedifferentiation by enhancing ribosomal biogenesis and protein synthesis 4. DNA methylation of the TERT promoter represents an epigenetic regulatory mechanism of telomerase activation in cancers 5. Clinically, TERT mutations associate with telomere-related bone marrow failure, dyskeratosis congenita, and pulmonary fibrosis. Activating TERT expression in aged cells mitigates aging hallmarks and neuroinflammation 2, while correcting TERT promoter mutations via base editing suppresses hepatocellular carcinoma growth 6, suggesting both therapeutic and diagnostic potential.