Deficiency of dystrophin, a 427-kDa subsarcolemma membrane protein, is responsible for Duchenne muscular dystrophy. The function of this protein is not clear but its subcellular distribution suggests that it is an important link between the cytoskeleton and the extracellular matrix, thus maintaining membrane integrity. The N-terminus of dystrophin was shown to bind actin in vivo and in vitro via two major actin binding sites. The role of dystrophin/actin interactions has been investigated and the results presented here demonstrate for the first time that the N-terminal part of dystrophin is able (i) to interact with G-actin monomers, and (ii) to slowly promote G->F actin transformation. This conversion was shown to be stimulated the presence of calmodulin in a calcium dependent manner. This is evidence that dystrophin is an anchor protein for actin involved in the control of membrane cell shape deformation and developing a calmodulin-calcium induced F-actin network, thus stiffening the myotube membrane cytoskeleton.