TERF1 (telomeric repeat binding factor 1) is a core component of the shelterin complex that binds directly to telomeric 5'-TTAGGG-3' repeats and negatively regulates telomere length 1. As a primary shelterin protein, TERF1 protects chromosome 8 from inappropriate DNA repair activation and regulates telomerase activity 2. The protein also plays roles in mitotic spindle regulation and telomeric D-loop disassembly 1. Mechanistically, TERF1 modulates TERRA (telomeric repeat-containing RNA) annealing to telomeres, actively repressing this process and failing to protect TERRA from RNase H digestion, contrasting with TRF2's stabilizing function 3. TERF1 expression increases in response to oxidative stress in inflammatory conditions 4. Clinically, TERF1 alterations associate with disease susceptibility. TERF1 amplification/upregulation predicts worse overall survival in prostate cancer 5, and elevated TERF1 expression correlates with survival outcomes across 24 cancer types 2. TERF1 gene variants link to male infertility risk 1, and a tissue-specific isoform (TERF1-tsi) is downregulated in testicular tumors 6. TERF1 also emerges as an autoantigen in systemic sclerosis patients 7.