CLIP2 is a CAP-Gly domain-containing linker protein that functions as a microtubule-associated protein involved in cytoplasmic microtubule organization. 1 The protein appears to link microtubules to dendritic lamellar bodies, specialized membranous organelles in neuronal dendritic appendages, and likely participates in brain-specific organelle translocation. CLIP2 binds microtubule plus-ends and associates with microtubule plus-end complexes through its CAP-Gly domain, positioning it as a key regulator of microtubule dynamics in neural tissues. Beyond its canonical neuronal functions, emerging evidence suggests CLIP2 has broader physiological roles. Recent studies demonstrate that CLIP2 (also referenced as CILP2) is significantly elevated in skeletal muscle during aging and in sarcopenia patients, where it negatively regulates glucose metabolism and myogenic differentiation. 1 CLIP2 overexpression suppresses myogenic proliferation markers (Ki67, PCNA, MyoD1) and impairs insulin sensitivity and glucose uptake through antagonism of Wnt/β-catenin signaling. Notably, CLIP2 interacts directly with Wnt3a protein, and CLIP2 knockdown enhances glucose metabolism, mitochondrial function, and muscle regeneration in aged mice. 1 These findings suggest CLIP2 has pleiotropic functions extending from neuronal microtubule dynamics to metabolic regulation in skeletal muscle, making it a potential therapeutic target for age-related metabolic disorders.