Ezrin (EZR) (EZR)

Ezrin is a member of the ERM (Ezrin-Radixin-Moesin) protein family that serves as a critical cross-linker between the plasma membrane and the actin cytoskeleton [1, 2]. It is essential for maintaining cell shape, polarity, and the organization of specialized membrane domains such as microvilli and ruffles [5, 9]. In the context of human disease, ezrin is a prominent driver of cancer metastasis; its overexpression and aberrant activation are strongly associated with increased cell motility, invasion, and poor clinical outcomes in various malignancies, including osteosarcoma and breast cancer [1, 11, 17]. Beyond oncology, ezrin is implicated in the pathogenesis of asthma through its role in airway epithelial repair and inflammation [6, 23]. Therapeutic development has focused on small molecule inhibitors, such as NSC305787 and NSC668394, which aim to disrupt ezrin's protein-protein interactions and suppress its pro-metastatic signaling [13, 14, 18]. Additionally, synthetic ezrin-derived peptides like HEP1 have been explored for their immunomodulatory properties in viral infections and inflammatory conditions [12, 15].

Other names

Villin-2Cytovillinp81VIL2CVILCVLHEL-S-105

Ezrin inhibitors typically function by disrupting the protein-protein interactions between the ezrin FERM domain and its binding partners, such as actin or membrane receptors like CD44 and EGFR, or by preventing its activation through phosphorylation at the Thr567 site [13, 14, 18]. This disruption leads to the inhibition of cell migration, invasion, and pro-survival signaling pathways like PI3K/AKT and Rho GTPases [1, 11, 19].