To dissect why D1R- and D2R-MSNs are differentially affected by HD, Lee et al. (2020) highlighted thousands dysregulated protein-coding genes implicated in OXPHOS, synaptic functioning and circadian entrainment by using translating ribosome affinity purification and snRNA-seq of D1R and D2R neurons of HD patients and mouse models (R6/2 and zQ175DN, a knock-in zQ175 line without neomycin cassette) (Franich et al., 2019). Here, DRD2 is linked to Huntington disease.