 DDX39B is a key regulator of immune tolerance, controlling the expression of many genes involved in MS susceptibility and immune function. It also affects splicing of FOXP3 introns, which contain C-rich polypyrimidine tracts and are highly sensitive to DDX39B levels. This suggests that DDX39B may be an important guardian of immune tolerance by controlling the expression of genes involved in autoimmunity. This article was authored by Minato Hirono, Gadiel Galaza Muñoz, Chloe Negasawa, and others.