Mice deficient in IL-22 or IL-22RA1 on a right open reading frame 2 (Riok2)-haploinsufficient background develop excess red blood cells (RBCs) and exhibit downregulated apoptosis in erythroid precursors, while exogenous supplementation with rIL-22 exacerbates phenylhydrazine-induced anemia, as evidenced by upregulated apoptosis and reduced numbers of RBCs. This evidence concerns the gene IL22RA1 and anemia.