Oligodendrocytes change shape during myelination, suggesting that correct modulation of cell polarity is essential to their function. Jarjour et al. showed that the protein Scribble, an evolutionarily conserved regulator of cell polarity, is increased in mouse oligodendrocytes as they differentiate. Oligodendrocyte-specific deletion of the gene encoding Scribble reduced developmental myelination in the CNS and impaired remyelination following a demyelinating lesion. This suggests that Scribble is an important modulator of oligodendrocyte function during development and repair.