While the exact functions of PI4KB in the nucleus remain to be determined, phosphoinositides are known to be involved in gene transcription, mRNA processing and chromatin remodelling.37 RAF1, a MAPKKK acting upstream of ERK, was found to be hyperphosphorylated in Huntington’s disease mice, which translates into an increased stability of the enzyme.22 Concordant with our data, a previous study has found increased activation of RAF1, and its upstream regulators, in Huntington’s disease cells and mouse models.38 Here, PI4KB is linked to juvenile Huntington disease.