HTT and Huntington disease: Studies in HD models have revealed alterations in HTT phosphorylation at S421 that could result from defects in Akt, the S421 kinase, or dysregulation of the phosphatases calcineurin (PP2B) and PP2A (Humbert et al., 2002; Metzler et al., 2010; Pardo et al., 2006; Warby et al., 2005).