Although abnormal SHH signaling was first observed in cerebellar cells isolated from the Ts65Dn mouse model of Down syndrome (Roper et al., 2006a), this model is trisomic for ∼60 genes that are not orthologs of human chromosome 21, raising the possibility that non-chromosome 21 orthologs could contribute to the cerebellar phenotypes observed in Ts65Dn mice (Duchon et al., 2022, 2011; Reinholdt et al., 2011). The gene discussed is SHH; the disease is Down syndrome.