{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Ezrin (encoded by the VIL2 gene) acts as a pivotal membrane–cytoskeleton linker that orchestrates diverse cellular processes by connecting plasma membrane proteins to filamentous actin. In several cancer models, ezrin expression is critical for metastasis by facilitating early survival of disseminated tumor cells and promoting cell motility; for instance, high ezrin levels correlate with enhanced metastatic potential and poor clinical outcome in osteosarcoma and rhabdomyosarcoma, where it modulates MAPK‐dependent survival signaling (."}, {"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 the vascular and inflammatory context, ezrin – together with its ERM relatives – links adhesion receptors such as VCAM‑1 to the actin cytoskeleton, thereby participating in the formation of endothelial docking structures that facilitate leukocyte adhesion and transendothelial migration ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ")."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Ezrin is rapidly recruited during dynamic membrane events: during bleb retraction, for example, ezrin is among the first proteins to associate with the plasma membrane to reestablish cortical actin networks, a function essential for the remodeling of cellular morphology and recovery of contractility ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ")."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, ezrin is a substrate for kinases such as LRRK2 in neuronal cells, with pathogenic mutations (e.g., G2019S) enhancing its phosphorylation. This modification alters the dynamics of filopodial actin structures and is linked to impaired neurite outgrowth, underscoring a key role in neuronal morphogenesis ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ")."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In fibroblasts, endothelin‑1 induces ezrin expression as part of a broader program that promotes a contractile, myofibroblast phenotype crucial for matrix remodeling during tissue repair ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "). In parallel, in tumor cells, the colocalization of ezrin with surface glycoproteins such as PA2.26 contributes to cytoskeletal reorganization and downregulation of cell–cell adhesion molecules, thereby facilitating invasion ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ")."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The interaction of ezrin with components of the CD44 complex also plays a critical role in directional cell motility, as phosphorylation‐dependent modulation of this binding governs the reorganization of actin and the formation of membrane protrusions necessary for migration ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "). Additionally, ezrin contributes to the structural integrity of specialized cortical domains, with binding partners such as EBP50 ensuring its active configuration at the apical membranes of polarized epithelial cells ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ")."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, ezrin is integrated into larger signaling assemblies that regulate receptor tyrosine kinase activity in carcinoma cells, and its role in maintaining an organized apical actin network is vital for intestinal barrier function ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "). In podocytes, altered ezrin distribution accompanies cytoskeletal disorganization linked to glomerular dysfunction ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "). \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore ezrin’s multifaceted role in linking membrane proteins to the actin cytoskeleton, thereby regulating cell adhesion, survival, motility, and signal transduction across diverse physiological and pathological settings.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chand Khanna, Xiaolin Wan, Seuli Bose, et al. 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