Merosin deficient congenital muscular dystrophy (LAMA2 disease) is an autosomal recessive disorder characterized by progressive wasting muscular dystrophy, dysmyelinating neuropathy and brain abnormalities. This disorder is caused by mutations in the <i>LAMA2</i> gene, which encodes for the laminin211, the primary component of the Schwann cell and muscle basal lamina. We recently identified Jab1 as a nuclear molecule downstream the laminin211 pathway and showed that Jab1 regulates Schwann cell behavior through the modulation of p27Kip1 levels. Interestingly, loss of Jab1 in Schwann cells results in a dysmyelinating neuropathy that phenocopies the neuropathy of LAMA2 disease. To evaluate whether Jab1 also plays a role in the pathogenesis of LAMA2 muscular dystrophy, we generated mice with conditional inactivation of <i>Jab1</i> in the muscle lineage through the MyoDi-cre transgene. Mice with deletion of <i>Jab1</i> in skeletal muscle (named Jab1-MscKO) showed progressive motor deficits, reduced lifespan and overt muscular dystrophy phenotype. Muscles appeared smaller in size and presented myopathic features such as reduced fiber diameter, presence of necrotic fibers, inflammatory cells, and fibrosis. The evaluation of satellite cell number showed a reduction of proliferating satellite cells, suggesting a defect of cell cycle progression. Muscle regeneration, induced by cardiotoxin injection, was significantly impaired in Jab1-MscKO mice. Jab1-MscKO muscles showed increased of p27Kip1 expression. Genetic deletion of <i>p27Kip1</i> in muscles of Jab1-MscKO mice revealed a mild, but not significant, amelioration of motor performances and muscle pathology, while reduced inflammatory infiltrates and ameliorated satellite cells cycling. Our results suggest that Jab1 in involved in the pathogenesis of LAMA2 muscular dystrophy, while p27Kip1 might influence the correct cell cycle progression of satellite cells.