LARGE is a glycosyltransferase known to glycosylate α-dystroglycan, a component of the dystrophin-associated glycoprotein complex. Spontaneous deletions in the Large gene (Largemyd and Largevls) result in muscular dystrophy accompanied by heart, brain, and eye defects. Another Large mouse mutant, enervated (Largeenr), is the result of a transgene integration event that disrupts Large gene expression. In addition to myodystrophy, enr mice have been shown to display peripheral nerve abnormalities, including altered axonal sorting resulting from Schwann cell defects, poor regeneration after nerve injury, and abnormal neuromuscular junctions. These data have provided new insight into our understanding of the function of LARGE and have suggested the possibility of involvement of substrates in addition to α-dystroglycan in the generation of the LARGE phenotype. The Large mutants are excellent models for addressing the importance of glycosylation in neuromuscular disease.