The sarcoglycans are transmembrane components of the dystrophin-glycoprotein complex, which links the cytoskeleton to the extracellular matrix in adult muscle fibers. Mutations in all four known sarcoglycan genes (alpha, beta, gamma, and delta) have been found in humans with limb-girdle muscular dystrophy. We have identified a novel protein, epsilon-sarcoglycan, that shares 44% amino acid identity with alpha-sarcoglycan (adhalin). We show that epsilon-sarcoglycan is a membrane-associated glycoprotein and document its expression by Northern blotting, immunoblotting, and immunofluorescence. In contrast to alpha-delta sarcoglycans, which are expressed predominantly or exclusively in striated muscle, epsilon-sarcoglycan is broadly distributed in muscle and nonmuscle cells of both embryos and adults. These results raise the possibility that sarcoglycan-containing complexes mediate membrane-matrix interactions in many cell types.