This BDNF-TrkB mediated downregulation of KCC2 is well-characterized and underlies impaired KCC2 activity in many neuropathologies (Liu et al., 2019a; Pradhan et al., 2019), which lends strength to the hypothesis that alterations in BDNF signaling underlie KCC2 dysfunction in HD. This evidence concerns the gene SLC12A5 and Huntington disease.