Genetic deficiencies of IKK2, RelA, and c-Rel or the combined deficiencies of RelA and c-Rel in Tregs revealed unexpected cell type-specific functions of the canonical NF-κB pathway in the development of Tregs and the maintenance of the Treg-suppressive phenotype during homeostasis and in tumor microenvironments. The gene discussed is REL; the disease is neoplasm.