Chromodomain on Y-like (CDYL) is a chromodomain protein that has sequence homology to members of the enoyl CoA hydratase family. Although the chromodomain of CDYL has been implicated in chromatin remodeling during mammalian spermatogenesis, the function of the Cdyl gene remains unclear. Recently, induced pluripotent stem cells (iPS cells) have been derived from somatic cells by the forced expression of several transcription factors. iPS cells resemble embryonic stem cells in many respects. Therefore, iPS cells represent a powerful tool for the study of gene function. In this study, we have investigated whether iPS cells derived from Cdyl-/- and Cdyl+/+ fibroblasts have different characteristics. Our results showed that both Cdyl-/- and Cdyl+/+ fibroblasts could be induced to become iPS cells, but the spontaneous neuronal differentiation capacity of Cdyl-/- iPS cells was much greater than that of the Cdyl+/+ iPS cells. These results provide some insight into the molecular function of the Cdyl gene, showing that it inhibited the neuronal differentiation of iPS cells.