Combination treatment consisting of lithium or L-690,330 with rapamycin results in enhanced clearance of mutant Htt and enhanced protective effects in cell and fly models of HD, compared to treatment with either drug alone (Sarkar et al., 2005, 2008), These effects are due to the additive effects of mTOR inhibition (by rapamycin) and the mTOR-independent phosphoinositol pathway regulation (by lithium and L-690,330) in enhancing autophagy (Sarkar et al., 2005). Here, HTT is linked to Huntington disease.