Ezrin (EZR) is a critical cytoskeletal linker protein that anchors actin filaments to the plasma membrane 1. In epithelial cells, EZR is essential for forming microvilli and membrane ruffles, and coordinates with PLEKHG6 for normal macropinocytosis. EZR functions as part of the ERM (ezrin-radixin-moesin) complex, which connects the plasma membrane to the cytoskeleton and is crucial for immune cell function 2. Mechanistically, EZR regulates RhoA, Rac1, and Cdc42 activation to control cell adhesion and migration 3. Phosphorylation-dependent activation enables calcium signaling and immune responses 2. EZR expression is regulated by long noncoding RNA EZR-AS1 through SMYD3-mediated histone methylation 4. Disease relevance is substantial: autosomal-recessive EZR mutations cause immunodeficiency with B-cell deficiency and impaired adaptive immunity 2. EZR is upregulated in breast cancer, where it promotes proliferation, invasion, and metastasis through EMT pathways 3. Similarly, elevated EZR-AS1 in lung adenocarcinoma correlates with increased cell proliferation and migration 5. EZR dysfunction also associates with Alzheimer's disease pathogenesis in metabolism-related subtypes 6. Clinically, EZR represents a potential therapeutic target for cancer metastasis and immunological disorders.