In skeletal muscle, syntrophins have four main isoforms: α-, β1-, β2-, and γ2-syntrophin.    β-dystrobrevin has been thought to play a structural role in the composition of the dystrophin-associated protein complex in the brain which differs from that in muscle. β-dystrobrevin coimmunoprecipitates with the dystrophin isoforms Dp71 and Dp140 in the brain. Dp140 is concentrated in the brain microvasculature while the Dp71 transcript is found throughout the brain but is particularly abundant in the dentate gyrus of the temporal lobe, and the olfactory bulb. The consequences of null mutation are known for humans and rodents in the case of dystrophin, utrophin, and α-dystrobrevin, and for nematode in the case of dystrophin and dystrobrevin. In human, the Duchenne muscular dystrophy is a well-known muscle disease which highlights the importance of dystrophin/ dystrobrevin protein to function of muscle tissue. Duchenne muscular dystrophy (DMD) is a fatal progressive disease of both cardiac and skeletal muscle resulting from the mutations in the DMD gene and loss of the protein dystrophin. The lack of dystrophin that causes Duchenne muscular dystrophy results in secondary loss of other dystrophin-complex components from the membrane. The loss of protein dystrophin ultimately leads to a lethal syndrome of skeletal and cardiac myopathy, stationary night blindness, mental retardation, a cardiac-conduction defect, and a subtle smooth-muscle defect. Some of these traits are also found in a subset of the limb-girdle muscular dystrophies that result from sarcoglycan defects. α-Dystrobrevin proteins were found absent in a heart that is highly susceptible to injury during cardiac stress. The dystrobrevin loss resulted from a weakening of dystrophin's interaction with the membrane-bound dystrophin-glycoprotein complex, and lead to a significant loss of membrane integrity.