Given that CKB is a strong positive modulator of KCC2 activity, where suppression of CKB activity leads to reduced KCC2 function (Inoue et al., 2006), it is possible that the depolarization of EGABA and Cl– dysregulation could be a result of the progressive downregulation of CKB in HD (Figure 5). The gene discussed is CKB; the disease is Huntington disease.