GlialCAM, a regulatory subunit of ClC-2 in glial cells and involved in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC), increases the activity of a ClC-2 mutant by affecting ClC-2 gating and by stabilising the mutant at the plasma membrane.
Mutations in the genes encoding the astrocytic protein MLC1, the cell adhesion molecule GlialCAM or the Cl(-) channel ClC-2 underlie human leukodystrophies.