GAS2 is a microfilament-associated protein that functions as a critical cytoskeletal regulator with dual interactions with actin filaments and microtubules 1. The protein contains calponin homology (CH) domains for actin binding and a GAR (Gas2-related) domain for microtubule binding 2, enabling it to mediate crosslinking and bundling of both cytoskeletal components through C-terminal-dependent dimerization 1. In the inner ear, GAS2 maintains microtubule bundles in supporting cells, providing mechanical stiffness necessary for sound transmission through the cochlea. Mechanistically, GAS2 regulates cellular processes including cell cycle progression, apoptosis, and senescence 3, partially through inhibition of Calpain-2, a calcium-dependent protease 3. The protein is cleaved by ICE-like proteases during apoptosis, inducing cytoskeletal rearrangements 4. Clinically, GAS2 mutations causing C-terminal truncation are linked to autosomal recessive deafness (DFNB125) due to disrupted cytoskeletal organization in auditory tissues 1. Beyond hearing loss, GAS2 exhibits context-dependent roles in cancer: it enhances chemosensitivity while promoting T-cell leukemogenesis through CXCR4/NOTCH1/c-MYC signaling 5, and regulates osteoarthritis progression through apoptosis regulation 6. GAS2 is located on chromosome 11.3-p15.2 4.