NONCANONICAL TRF2 activity in muscle stem cells orchestrates skeletal muscle regeneration independently of classical telomere dysfunction. Skeletal muscle repair relies on resident satellite cells that undergo dynamic cell-state transitions to reconstruct damaged myofibers following traumatic injury or chronic pathology. Noncanonical Roles of TRF2 in Muscle Stem CellsUnlike canonical models in other adult stem cell niches, deleting TRF2 in muscle stem cells does not trigger telomere attrition, end-to-end chromosome fusions, cellular senescence, or p53-dependent apoptotic pathways. Dystrophic mouse models featuring deletion of TRF2 in muscle stem cells exhibit accelerated pathology, displaying severe muscle atrophy, progressive spinal kyphosis, extensive diaphragm damage, and premature mortality within 28 weeks. TRF2 couples muscle stem cell identity to regenerative repair.