The ERM (Ezrin, Radixin and Moesin) proteins are highly conserved paralogues with overall 73-81% sequence identity in human. They are involved in maintaining cell cortex and in cell signaling pathways due to their ability to interact with both the plasma membrane and the actin cytoskeleton. Each of the ERM proteins is characterised by three domains: the ~300 residues FERM (band Four-point-one, Ezrin, Radixin and Moesin) domain at the N-terminus, the ~200 residues α-helical domain, and the ~100 residues C-terminal domain. It is known that ERM proteins exist in two states: the dormant state and the active state. In the dormant state, they are biologically inert as the relevant binding sites on both FERM and C-terminal domains are masked by intramolecular interactions between the three domains. In the active state, the FERM domain forms interface with the plasma membrane and binds to the cytoplasmic extensions of membrane proteins, while the C-terminal domain binds to the actin cytoskeleton.

The activation of ezrin involves both binding to phosphatidylinositol 4,5-biphosphate (PIP₂) and phosphorylation of a conserved threonine residue in the C-terminal domain (Thr567). Comparison between crystal structures of full-length ezrin and FERM domain of ezrin reveals structural changes upon ezrin activation. The structures of full-length ezrin are missing the α-helical domain due to limited proteolysis that occurred without the addition of protease during crystallisation.