Telomerase reverse transcriptase as a core regulator of brain health.

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, the holoenzyme whose activity maintains telomeres. Beyond this canonical role, emerging evidence indicates that TERT participates in nontelomeric programs with broad relevance to brain health. TERT can function as a transcriptional co-regulator of genes linked to neuronal viability, synaptic plasticity, and neurodegeneration. During aging and in neurodegenerative states, the TERT locus becomes epigenetically repressed, resulting in altered gene expression programs relevant to neuronal resilience. Genetic and pharmacologic restoration of physiological TERT levels reverses multiple aging phenotypes and mitigates molecular and pathological features associated with neurodegenerative disorders, including Alzheimer's disease. In this opinion article, we synthesize emerging evidence that positions TERT as a central coordinator of brain health and disease.