We found that REST and CoREST specifically target genes encoding a number of Htt interacting proteins in distinct neuronal subtypes (CHOLNs, GABANs, and GLUTNs but not MSNs) including Hip2, which is a ubiquitin conjugating enzyme involved in polyglutamine induced cell death, Ift57 (Hippi), which regulates apoptosis, and Prpf40b, which is a spliceosomal factor also associated with methyl CpG binding protein 2 (Mecp2) and Rett syndrome. Here, PRPF40B is linked to atypical Rett syndrome.