One function of the SG-SSPN subcomplex is to stabilize ␣-DG at the sarcolemma (Holt et al., 1998). By examining extraction of ␣-DG with SDS, we show that disruption of proper SG-SSPN protein interactions within the sarcolemma of SSPN-Tg muscle results in destabilization of ␣-DG. The role of ␣-DG in organization of the extracellular matrix has been well-established (Brown et al., 1999;Henry and Campbell, 1998;Henry et al., 2001;Kanagawa et al., 2005). We now show that SSPN overexpression disrupts formation of the extracellular matrix, as revealed by uncoupling of perlecan, laminin and collagen VI co-localization and as seen by electron microscopy. Laminins represent one of the major components of the extracellular matrix and mutations in the LAMA2 gene, which encodes laminin-␣2 chain, cause congenital MD (Allamand et al., 1997;Helbling-Leclerc et al., 1995;Miyagoe-Suzuki et al., 2000). Although the DGC is normally expressed in mouse models with defects in laminin (dy/dy, dy w /dy w , dy 3k /dy 3k , dy Pas /dy Pas , dy 2j /dy 2j ; dy = Lama2), the linkage between the extracellular matrix and the cytoskeleton is disrupted (Besse et al., 2003;Guo et al., 2003;Kuang et al., 1998;Miyagoe et al., 1997;Sunada et al., 1994;Xu et al., 1994). We provide **data** to demonstrate that the extracellular matrix, including laminin, exhibits abnormal structure in phenotypic SSPN-Tg muscle. Taken together, our **data** support a necessary role for SSPN in organizing proteins within the DGC and in assembly of the extracellular matrix.