Interestingly, BPAG1a is also a binding partner of endocytic vesicle proteins called transmembrane protein 108 and clathrin. The importance of the various BPAG1 isoforms is best attested by the dramatic consequences observed in cases of genetic defects of BPAG1. Naturally occurring mutations as well as engineered inactivation of Dst in mice cause dystonia musculorum, a disease characterized by sensory and motor VX-661 neuron degeneration, and early death. In humans, a pathogenic mutation affecting the MTBD of BPAG1a/b results in sensory autonomic neuropathy with dysautonomia, severe psychomotor retardation, and early death, while disruption of BPAG1a/b due to a chromosome breakpoint in the middle of one of the DST gene copies, is associated with encephalopathy, motor and mental retardation, and visual impairment. Dst-null mice showed also discrete signs of skin blistering as a result of an impaired attachment of keratin IFs to hemidesmosomes in basal keratinocytes due to the absence of BPAG1e. In humans, by analogy, homozygous nonsense DST mutations affecting BPAG1e result in epidermolysis bullosa simplex with fragility of basal keratinocytes and skin blistering. In skeletal muscle and cardiac tissues, BPAG1b is found colocalized with Z-discs, intercalated discs, and sarcolemma, but not with Tyrphostin AG 879 myosin and, surprisingly, actin. Furthermore, dt mice exhibit an intrinsic muscle weakness, increased muscle fatigability and sarcolemmal fragility, and an altered myotube cytoarchitecture, suggesting that BPAG1b has important roles in muscles. In this study we sought to gain better insight into the complexity of BPAG1 isoforms and their role in MT organization and stabilization in the mouse myoblast cell line C2.7. We have identified novel mouse BPAG1a/b isoforms due to alternative splicing of the end of their pre-mRNA affecting the C-tail of the proteins. By using siRNA-mediated Dst silencing, we further characterized the impact of BPAG1 isoforms on MT stability, cytoskeletal organization, cell migration, vesicular transport and cell adhesion of C2.7 myoblasts. The MTBD is composed of a GAR domain that co-localizes with and stabilizes MTs and a GSR-repeat domain that is able to bundle MTs in transfected COS-7 cells.