Levels of S13-phosphorylated HTT are reduced while total full-length (∼350 kDa) mouse HTT abundance is increased with IKKβ knockout in striatum, demonstrating that IKKβ is a relevant striatal HTT S13 kinase in vivo. Male R6/1 (HD) and NT WT controls, both containing the tamoxifen-inducible Cre and floxed alleles of IKKβ, were treated with tamoxifen or oil vehicle control during week 10 and killed at week 16. IKKβ normalized to loading control α-tubulin was significantly reduced in 16-wk striatum of HD and NT mice with tamoxifen treatment over oil control in whole-cell lysate (A–C). Anti-HTT phosphoserine 13 (pS13) antibody was used to immunoprecipitate phosphorylated full-length mouse HTT which was then detected by Western blot with anti-total HTT antibody. Levels of pS13-HTT were significantly reduced relative to total HTT with IKKβ knockout in HD and NT controls, while levels of total HTT normalized to α-tubulin were significantly increased (A–C). Western images (A and B) were quantitated using Scion software (C). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 values represent means ± SEM. Statistical significance was determined by paired t test.