Neural stem cells/ neural progenitors (NSC/NP) are the basic cellular constituent of neural development, giving rise to all the sub cells types in the brain. Regulation of NSC/NP fate and function occur at multiple levels including post-translational modifications by the ubiquitin pathway. Deubiquitylating enzymes play a central role in brain development by opposing the posttranslational modification imposed by the ubiquitin system on targeted protein. It has been shown that deubiquitylating enzyme Usp9x, a putative stemness gene, has an essential role in brain development. Ablation of Usp9x from the NSC/NPs in a developing mouse brain resulted in prenatal lethality signifying its importance in brain development. In addition, ectopic expression of Usp9x in embryonic stem cell derived NPs, promotes their self-renewal and polarity. More detailed histological analysis conducted on the Usp9x knockout (KO) NSC/NPs revealed that both adhesion and polarity were disrupted at E12.5. However, most markers of both adhesion and polarity in the KO NPs were recovered at later developmental stages (E14.5). In contrast, the adherens junction structural protein, β-catenin, which is also a substrate of Usp9x, showed an increased expression level in the basolateral membrane and cytoplasm of the Usp9x-null NPs in both stages. The cellular consequences included a significant increase in abventricularly proliferating NPs in the KO brains, implying an alteration in the NP differentiation or spatial expression. This study reveals how posttranslational modification by a substrate-specific deubiquitylating enzyme contributes to NSC/NP fate by regulating its cell adhesion and polarity. The finding of this study will aid out understanding of the molecular mechanisms underlying NSC/NP fate determination.