Mutations in the X-linked gene PCDH19 are the cause of PCDH19-clustering epilepsy, an infantile-onset disorder characterized by seizures and intellectual disabilities. Although several intra and extracellular functions of PCDH19 have been identified, the spatiotemporal impact of Pcdh19 deletion in vivo is poorly understood. To investigate the consequences of eliminating Pcdh19 in specific cell and brain regions, we generated a novel Pcdh19 floxed mouse with a GFP reporter (Pcdh19-cKO-GFP). Using Pcdh19-cKO-GFP and Syn1-Cre mouse lines we demonstrated that Pcdh19 elimination in neurons leads to abnormal hippocampal neurogenesis and impaired mouse behaviour. To assess the impact of region-specific elimination of Pcdh19 on brain physiology we used a Gfap-Cre mice line. Specific Pcdh19 deletion in the hippocampus resulted in increased neurogenesis and decreased memory formation. Finally, we assessed the feasibility of using our conditional mouse model for stage-specific Pcdh19 elimination during embryogenesis using a Dox-inducible Cre-deletor line. Taken together, these results demonstrate the utility of our unique Pcdh19-cKO-GFP mouse model to investigate PCDH19 function in brain physiology and pathology.