Growth arrest specific 2 (GAS2) is a multifunctional gene encoding a protein that has a pivotal influence on various cellular processes. It is involved in cytoskeletal regulation, cell cycle progression, apoptosis, and senescence. GAS2 also plays a role in the crosstalk between microtubules and actin through interactions with end-binding proteins [5,6]. It can regulate the cellular activity of Calpain-2, a calcium-dependent protease, by acting as an endogenous inhibitor [6].

In leukemic cells, the GAS2-Calpain2 axis is required for their growth. Silencing GAS2 in THP-1 and Jurkat cells led to elevated Calpain activity, decreased cellular growth, and inhibition of colony-forming cell production, and these effects could be rescued by GAS2 re-expression. Also, GAS2 silence prevented tumor formation of THP-1 cells in nude mice. GAS2 interacted with Calpain2 rather than Calpain1 in these cells [1]. In T-cell acute lymphoblastic leukemia (T-ALL), GAS2 promoted leukemogenesis through interaction with CXCR4 to activate NOTCH1/c-MYC, and GAS2 silencing impaired T-cell leukemogenesis and decreased leukemic cell infiltration [3]. In pediatric T-ALL cells, GAS2 promoted cell proliferation and invasion, suppressed apoptosis, and activated the Wnt/β-catenin pathway [4]. In cochlear supporting cells, mutations in GAS2 led to hearing loss due to disorganization and destabilization of microtubule bundles, altering cochlear micromechanics [2].

In conclusion, GAS2 is crucial for multiple biological processes. Studies using cell-based models and in vivo models (such as nude mice for leukemic cell tumor formation) have revealed its significance in leukemogenesis and hearing function. Understanding GAS2's functions provides insights into the molecular pathogenesis of hematological malignancies and potential approaches for treating these diseases, as well as the mechanisms underlying hearing loss.