Moesin (membrane-organizing extension spike protein, pronounced mó ez in) has previously been isolated from bovine uterus and characterized as a possible receptor protein for heparan sulfate. We now have cloned and sequenced its complete cDNA, which represents a single 4.2-kilobase mRNA encoding a protein of 577 amino acids. It contains no apparent signal peptide or transmembrane domain. In addition, the protein shows significant sequence identity (72%) to ezrin (cytovillin, p81), as well as similarity to protein 4.1 and talin. All of the latter proteins have been postulated to serve as structural links between the plasma membrane and the cytoskeleton. A similar role for moesin is implied by structure and domain predictions derived from the cDNA-deduced peptide sequence. Furthermore, our data indicate that moesin is identical to the 77-kDa band that copurifies with ezrin in its isolation from human placenta [Bretscher, A. (1989) J. Cell Biol. 108, 921-930].