CLCN4 and Intellectual disability: Hu et al. (2015), analyzing X-linked intellectual disabilities, identified five different mutations in the ClC-4 gene in five families. Currents of ClC-4 proteins carrying each of these mutations were much smaller or even absent compared to wild-type ClC-4. Moreover, C1C-4 depletion in cultured hippocampal neurons, affected neuronal differentiation; the cells displayed a 30% reduction of neuritic outgrowth and branching (Hu et al., 2015).