Lingo-1 is a 614-amino acid protein that plays an important role in the negative regulation of myelination by oligodendrocytes in the central nervous system (CNS). Lingo-1 is a nervous system-specific transmembrane protein that interacts with NgR1 and p75 to make up a receptor complex that binds to Nogo, a protein that inhibits axonal regeneration. Reduction of Lingo-1 activity downregulates RhoA (a protein related to cytoskeleton regulation) activity, promotes oligodendrocyte differentiation, and increases axonal myelination in neuronal tissues. Conversely, overexpression of Lingo-1 activates RhoA and inhibits oligodendrocyte differentiation and myelination. Lingo-1 up-regulation may be a characteristic of activity-induced neural plasticity responses. Lingo-1 may be a critical deterrent of myelin and nerve fiber repair in multiple sclerosis, an inflammatory disease that causes gradual destruction of myelin in the CNS.