The well-known alterations in BDNF-TrkB signaling in HD (Plotkin et al., 2014), combined with the regulatory effects of BDNF-TrkB signaling on KCC2 (Lee-Hotta et al., 2019; Rivera et al., 2002), open the possibility that impaired BDNF-TrkB signaling leads to altered Cl− homeostasis preferentially in D2 MSNs, playing a causal role in their enhanced susceptibility in HD. This evidence concerns the gene SLC12A5 and Huntington disease.