In the healthy brain, neuronal activity can influence OPC proliferation, differentiation, and myelination to facilitate adaptive myelin changes in active circuits. However, in diseases such as high-grade glioma, these mechanisms of plasticity may be hijacked to promote cancer progression, becoming maladaptive. In disease of white matter degeneration, the mechanisms of adaptive myelination may be compromised resulting in persistent demyelination or may be able to be harnessed to regenerate lost myelin.