ezrin

Ezrin is a cytoskeletal linker protein that connects the plasma membrane to the actin cytoskeleton. It is the founding member of the ezrin-radixin-moesin (ERM) family and is encoded by the EZR gene in humans. Ezrin is widely expressed and is particularly enriched at apical membranes, microvilli, and areas of dynamic membrane–cytoskeleton interaction, including sites of cell adhesion and migration.

structurally, ezrin contains an N-terminal FERM domain that binds membrane proteins and a C-terminal actin-binding domain. In its resting state, ezrin adopts a closed, autoinhibitory conformation. Activation involves binding to phosphatidylinositol 4,5-bisphosphate (PIP2) in the membrane, followed by phosphorylation at threonine 567 to stabilize the open, active form. This enables the protein to link transmembrane proteins to actin.

Ezrin functions to tether membrane proteins such as CD44 and certain integrins to the actin cytoskeleton, thereby organizing membrane domains, supporting cell shape and polarity, and facilitating adhesion, migration, endocytosis, and vesicle trafficking. It localizes to microvilli in epithelial cells and to dynamic cortical structures in migrating or proliferating cells, where it participates in signaling and cytoskeletal remodeling.

Regulation and clinical relevance: ezrin activity is controlled by phosphorylation and interactions with lipids and partner proteins, leading to context-dependent localization and function. Dysregulated ezrin expression or function has been associated with cancer progression and metastasis in several tumor types, and ezrin is studied as a potential prognostic marker and therapeutic target in certain cancers. In normal biology, it contributes to tissue integrity, cellular communication, and developmental processes.