Disease-causing missense (and other in-frame) mutations can exert their deleterious effects at the cellular level through multiple mechanisms. A pathogenic mechanism involves the addition of a novel N-linked glycan. Up to 1.4% of known disease-causing missense mutations are predicted to give rise to gains-of-glycosylation. For some of these mutations, the novel glycans have been shown to be both necessary and sufficient to account for the deleterious impact of the mutation. The chemical complementation of cells from patients in vitro with various modifiers of glycosylation has been demonstrated and raises the possibility of specific chemical treatments for patients bearing gain-of-glycosylation mutations.