Expression of the giant protein Ahnak has been reported in endothelial cells of the blood brain barrier and in non-neuronal cells including myelinating Schwann cells. However, the function of Ahnak in neurogenesis has not been determined. In the present study, we report for the first time the effects of Ahnak on adult hippocampal neurogenesis using Ahnak(-/-) mice. Proliferating cells were labeled with BrdU for a 30-day period before sacrifice. In Ahnak(-/-) mice, the incorporation of BrdU with NeuN (Neuronal Nuclei) increased significantly in both the subgranular zone and the granular cell layer of the dentate gyrus. In addition, Ahnak(-/-) mice displayed increased Doublecortin-immunoreactive neuroblasts compared with wild-type controls. Taken together, Ahnak deficiency plays a positive role for hippocampal neurogenesis in adult mice because proliferating cells were increased in Ahnak(-/-) mice and advanced to mature neurons. These findings suggest that Ahnak might be involved in modulating the differentiation of newly generated cells into neuronal or non-neuronal cells.