TELO2 (telomere maintenance 2) is a key regulator of the DNA damage response (DDR) that functions as a component of the conserved TTT complex alongside TTI1 and TTI2 1. The TTT complex stabilizes phosphatidylinositol 3-kinase-related protein kinases (PIKKs), including mTOR, ATM, and ATR, by facilitating their assembly with the R2TP complex and heat shock protein 90 chaperone 2. TELO2's C-terminal domain mediates interaction with TTI1 and recruitment of ATM, with these regions essential for cell survival under ionizing radiation stress 2. Beyond DNA damage response, TELO2 promotes assembly and maintains activity of mTORC1 and mTORC2 complexes, regulating cell growth and survival 1. Biallelic TELO2 variants cause You-Hoover-Fong syndrome (YHFS), an autosomal recessive neurodevelopmental disorder characterized by global developmental delay, intellectual disability, microcephaly, dysmorphic facial features, movement disorders, and ocular involvement including cataracts and cortical visual impairment 3 4 5. Additional features include cardiac malformations, epilepsy, and hearing loss 3. TTT complex dysfunction impairs mTOR pathway activity, improved by rapamycin treatment 1. In high-grade gliomas, TELO2 overexpression correlates with shorter patient survival 6, and TELO2 represents a druggable target for conditions involving Wnt/β-catenin pathway dysregulation 7.