In the current study, we engineered transgenic mice to overexpress SSPN protein in skeletal muscle as an alternate approach to investigate the function of SSPN. SSPN transgenic (SSPN-Tg) mice exhibit a severe phenotype that is much more similar to laminin-deficient muscle (Besse et al., 2003;Guo et al., 2003;Kuang et al., 1998;Miyagoe et al., 1997;Xu et al., 1994). Taken together, our **data** support a necessary role for SSPN in organizing proteins within the DGC and in assembly of the extracellular matrix.