Huntington’s disease (HD) and X linked dystonia parkinsonism are basal ganglia diseases, which have in common a decrease in TAF1 expression. Transgenic HD mouse model (R6/1) show diminished TAF1 levels together with an imbalance in usage of an alternative 3’ splicing site of TAF 1, which leads to an increase of isoforms with the long version of exon 5 (TAF1-e5L), which carry a putative prolyl hydroxylase (PHD) dependent degradation motif. This alteration is corrected by SREK1 overexpression, and leads to behavioral and neuropathological recovery of R6/1 mice. We aim to analyze TAF1 splicing variants that affect the stability of the protein in HD. We analyzed the stability of TAF1 isoforms through plasmid transfection in neuroblastoma cells, and by in vivo administration of the PHD inhibitors DMOG and roxadustat in WT and R6/1 mice. TAF1-e5L protein is less stable than exon 5 short isoform, and DMOG selectively increases TAF1-e5L levels in cells. DMOG administration increases total TAF1 levels in WT mice and leads to an improvement of R6/1 mice performance in the vertical pole test. Long-term roxadustat treatment also induces an improvement in the vertical pole test as well as an attenuation of hypokinesia. However, the main motor deficits are not rescued. In summary, TAF1-e5L splicing variant generates a less stable product that may account for TAF1 deficiency in HD. PHD inhibitors are able to increase TAF1 levels, and induce a modest behavioral benefit in HD mouse models.