In HD, striatal MSNs have elevated levels of extracellular K+, due to abnormal astrocyte-mediated K+ homeostasis via impaired Kir4.1 channels, leading to neuronal excitability (Figure 5; Tong et al., 2014), which could lead to a reversal in the direction of ion transport via KCC2 to mitigate neuronal K+-mediated excitability. This evidence concerns the gene SLC12A5 and Huntington disease.