Dissecting the role of the thalamus in neuropsychiatric disorders requires new models to analyze complex genetic interactions. In this issue of Cell Stem Cell, Shin et al. use patient-derived thalamocortical organoids to investigate 22q11.2 microdeletion impact on thalamic development, revealing significant transcriptional dysregulation linked to psychiatric disorders. Dissecting the role of the thalamus in neuropsychiatric disorders requires new models to analyze complex genetic interactions. In this issue of Cell Stem Cell, Shin et al. use patient-derived thalamocortical organoids to investigate 22q11.2 microdeletion impact on thalamic development, revealing significant transcriptional dysregulation linked to psychiatric disorders.