Besides testing whether Ryk cytotoxicity might be modulated by mammalian Wnt ligands or Ryk inhibitory antibodies [33] and studying whether an excess of the Ryk-ICD fragment might tether β-catenin away from FOXO, it will be interesting to identify the FOXO3a transcriptional targets that may be deregulated by Ryk in mutant polyQ neurons and understand how this may impact brain longevity mechanisms as the pathogenic process develops in HD. This evidence concerns the gene RYK and Huntington disease.