Ezrin is a member of the ERM (Ezrin, Radixin, Moesin) protein family and serves as a crucial linker between the cell membrane and the actin cytoskeleton. Phospho-Ezrin (Tyr354), also annotated as Tyr353 in early literature, is a tyrosine-phosphorylated active form of ERM scaffold protein Ezrin encoded by the EZR gene. Triggered by HGF receptor tyrosine kinase, this modification unlocks Ezrin's autoinhibited conformation and enables high-affinity binding to the p85 regulatory subunit of PI3K. It sustains PI3K/Akt survival signaling, suppresses epithelial apoptosis, and drives cytoskeleton remodeling for cell migration and tubulogenesis. Unique from Thr567-phosphorylated Ezrin at cell membranes, p-Ezrin (Tyr354) translocates into nuclei in osteosarcoma and lung cancer. Its elevated nuclear expression correlates with tumor invasion, metastasis, and poor clinical prognosis, marking it a promising malignant progression biomarker. (PMID: 10377409, 20348881)