Our demonstration of altered t-tubule structure and the elevated Ca2+-sensitive pathways in dysferlin-null muscle is consistent with reports that both are disrupted in dysferlinopathies (Selcen et al., 2001; Campanaro et al., 2002; Suzuki et al., 2005; Demonbreun et al., 2014). Here, DYSF is linked to neuromuscular disease caused by qualitative or quantitative defects of dysferlin.