PROJECT SUMMARY Rare diseases are a leading cause of morbidity and mortality in children and adults that frequently have a genetic etiology, but specific treatments are only beginning to emerge. Among more than 10,000 individual rare diseases, less than 5% have a specific treatment, in part because the affected protein is understudied. FOXP1 is an understudied forkhead box transcription factor that urgently needs investigation to reveal its impact to human health as a therapeutic target. We have identified prominent cerebellar hypoplasia in patients with heterozygous variants in the FOXP1 gene, but the cellular and molecular mechanisms driving this abnormality have not been studied. In Aim 1, we will characterize FOXP1 cell type and spatiotemporal expression and visualize microvascular architecture in human cerebellar development using high resolution optical imaging. In Aim 2, we will construct FOXP1 cell-type-specific gene regulatory networks using single cell genomic assays. The results from these experiments will provide foundational data for investigating pathological development of FOXP1 syndrome.