This study provides evidence that ING2 is an essential regulator of mammalian spermatogenesis by showing that: 1) testes express high levels of ING2 (Fig. 1A,B, Fig. S1); 2) genetic knockout of Ing2 causes a spermatogenesis defect and male infertility in mice (Figs 1C–G, 2A–F and Table 1); and 3) decreased ING2 expression is highly associated with defective spermatogenesis and male infertility in humans (Table 2). This evidence concerns the gene ING2 and male infertility.