{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Growth arrest‐specific 2 (GAS2) is a multifunctional protein originally identified as being induced during growth arrest. Multiple studies have demonstrated that GAS2 plays important roles in regulating cellular homeostasis by modulating both cytoskeletal dynamics and cell death pathways. In several cell‐based systems, the GAS2 protein was shown to inhibit calpain protease activity, thereby affecting the stability and activity of key signaling molecules such as β‐catenin and sensitizing cells to p53‐dependent apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its apoptotic and growth‐inhibitory functions, GAS2 and its family members also serve as cytoskeletal crosslinkers. Their unique domain organization—with distinct actin‐binding (calponin homology) and microtubule‐binding (GAR) domains—enables them to mediate the crosstalk between filamentous actin and microtubules, thereby contributing to the stabilization, bundling, and dynamic regulation of the cytoskeleton."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " This cytoskeletal function is critical for maintaining cell shape and polarity, as exemplified in inner ear supporting cells where GAS2‐mediated microtubule bundling is essential for proper mechanical support and sound transmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond these roles, GAS2 influences tissue remodeling and cell cycle regulation in distinct physiological and pathological contexts. In the ovary, GAS2 is necessary for proper tissue organization during folliculogenesis, with its loss perturbing oocyte cyst breakdown and basal lamina integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In cancer, altered GAS2 expression has been linked to tumor suppression—for example, in hepatocarcinogenesis, where GAS2 expression promotes p53‐dependent apoptosis and senescence to counteract oncogenic signals—and in colorectal cancer, where its levels may correlate with cell growth regulation and chemosensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Taken together, GAS2 functions as a critical integrator of signals that control both cell survival and cytoskeletal organization. A recent comprehensive review has further underlined the diverse roles of the GAS2 family—including GAS2 itself, GAS2-like proteins, and related isoforms—in processes ranging from apoptosis and cell cycle regulation to cytoskeletal reorganization and cancer development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francesca Demarchi, Cosetta Bertoli, Tamara Copetti, et al. 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