A model of selective degeneration of striatal neurons in HD. The idea that Rab11 activation is achieved by a protein complex composed of HTT, Kalirin, and TRAPPII was based on our recent studies (Ke et al., 2020; McClory et al., 2018; Wang et al., 2020). Mutant HTT compromises the Kalirin–TRAPPII complex in activating Rab11 on endosomal membranes (1), thereby impeding XK recycling back onto neuronal surfaces (2) and reducing XK-mediated import of Mn into neurons (3). Constant deficiency of Mn along with the chronic decline of functions of other Rab11-regulated trafficking proteins render the dysfunction of striatal neurons (4) and eventually leads to degeneration of striatal neurons and atrophy of the striatum (5).