GlialCAM (also named HepaCAM) is a cell adhesion molecule expressed mainly in glial cells from the central nervous system and the liver. GlialCAM plays different roles according to its cellular context. In epithelial cell lines, overexpression of GlialCAM increases cell adhesion and motility but also inhibits cell growth in tumor cell lines, leading to senescence. In glial cells, however, its function is quite different. GlialCAM acts a regulator of subcellular traffic of MLC1, a protein with unknown function involved in the pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare neurological condition. Moreover, GlialCAM itself has been found to be responsible for some of the cases of this disease. Additionally, GlialCAM also works as an auxiliary subunit of the chloride channel ClC-2, regulating its targeting to cell-cell junctions and modifying its functional properties. In summary, GlialCAM has different functions not only related to its adhesive nature, and defects in these functions lead to neurological disease.