As dysregulated Ca2+ signaling at the t-tubule is known to underscore contraction-induced damage in Duchenne muscular dystrophy (Yeung et al., 2005; Fanchaouy et al., 2009; Shkryl et al., 2009) and dysferlin is preferentially localized within the t-tubule, we hypothesized that the t-tubules may be especially susceptible to damage in dysferlinopathy, and that a Ca2+ -dependent process may play a critical role in disease progression. The gene discussed is DYSF; the disease is neuromuscular disease caused by qualitative or quantitative defects of dysferlin.