Schematic representation of the proposed mechanism of the vimentin effect on mutant Htt aggregation. A. In HD, mutant Htt and dopamine stimulation may activate ROCK, which in turn phosphorylates vimentin at Ser71 and Ser38 leading to IRBIT sequestration, reduced interaction of IRBIT with IP3R1, and activation of IP3R1. Mutant Htt expression and aggregation may increase aggresome formation enhancing IRBIT sequestration. B. Blocking vimentin phosphorylation by ROCK inhibitors may lead to reduced IRBIT sequestration by vimentin and consequently to decreased accumulation and aggregation of the pathogenic polyQ protein.