Several findings suggest that CLCN2 downregulation in MS may reflect altered WM integrity and/or contribute to the mechanisms of myelin destruction: first, ClCN2−/− mice exhibit abnormal WM morphology (Blanz et al., 2007); second, loss-of-function CLCN2 mutations lead to leukodystrophy; third, loss of cell adhesion molecule GlialCAM, which binds to ClC-2 in glia, is associated with leukodystrophy (Jeworutzki et al., 2012; Hoegg-Beiler et al., 2014). Here, CLCN2 is linked to leukodystrophy.