The article reviews the regulation of telomerase reverse transcriptase (TERT) in cancer. TERT, a key component of telomerase, is crucial for maintaining telomere length and preventing cellular senescence. Abnormal activation of TERT occurs in most cancer types, leading to immortalization and tumor formation. The regulation of TERT involves transcriptional factors, post-translational modifications (PTMs), and co-interacting proteins. Transcriptional regulation includes promoter mutations and chromosomal rearrangements, which lead to TERT overexpression. PTMs such as phosphorylation, ubiquitination, and SUMOylation affect TERT's stability, localization, and activity. Co-interacting proteins modulate TERT's assembly, trafficking, and recruitment to telomeres. Additionally, TERT exhibits non-canonical functions, influencing angiogenesis, epithelial-to-mesenchymal transition (EMT), and immune response. Current and future pharmacological strategies targeting TERT or telomerase, including small molecule inhibitors and vaccines, show promise in cancer treatment. However, further research is needed to optimize these approaches and reduce adverse effects.The article reviews the regulation of telomerase reverse transcriptase (TERT) in cancer. TERT, a key component of telomerase, is crucial for maintaining telomere length and preventing cellular senescence. Abnormal activation of TERT occurs in most cancer types, leading to immortalization and tumor formation. The regulation of TERT involves transcriptional factors, post-translational modifications (PTMs), and co-interacting proteins. Transcriptional regulation includes promoter mutations and chromosomal rearrangements, which lead to TERT overexpression. PTMs such as phosphorylation, ubiquitination, and SUMOylation affect TERT's stability, localization, and activity. Co-interacting proteins modulate TERT's assembly, trafficking, and recruitment to telomeres. Additionally, TERT exhibits non-canonical functions, influencing angiogenesis, epithelial-to-mesenchymal transition (EMT), and immune response. Current and future pharmacological strategies targeting TERT or telomerase, including small molecule inhibitors and vaccines, show promise in cancer treatment. However, further research is needed to optimize these approaches and reduce adverse effects.