Dissecting Dystrophies Defects in α-dystroglycan lead to various congenital muscular dystrophies, and its ability to bind to extracellular matrix (ECM) is dependent on formation of a specific O-linked sugar structure. Previous efforts to understand the molecular mechanisms underlying α-dystroglycan's ability to bind to the ECM led to the identification of a phosphorylated O -mannosyl trisaccharide on α-dystroglycan and to the demonstration that addition of this residue is a prerequisite for formation of the ligand-binding motif. However, the biosynthetic pathway that leads to production of the phosphorylated O -mannosyl glycan has not been delineated. Yoshida-Moriguchi et al. (p. 896 , published online 8 August) elucidate the functions of three genes recently found to cause dystroglycan-related disorders and explain the defects in the production of the phosphorylated O -mannosyl glycan that underlie the pathologies of patients with the relevant mutations.