Epigenetic mechanisms are leveraged throughout development to maintain gene activity states. The polycomb group family of proteins are an essential class of epigenetic regulator, critical for neurodevelopment. Polycomb Repressive Complex 1 alters chromatin through the deposition of H2A ubiquitination(H2AK119ub1), in contrast, Polycomb repressive deubiquitinase (PR-DUB) complex removes H2AK119ub1. The antagonistic relationship maintains the appropriate balance of H2AK119ub within the cell to control gene expression. MBD5 plays an important role in stabilizing the PR-DUB. Mutations in MBD5 gene cause a rare syndrome termed MBD5- associated neurodevelopmental disorder(MAND) and are associated with intellectual disability and social communication deficits. Although it is known that MBD5 is necessary for neurodevelopment, its function is poorly understood. I hypothesise that mutations in MBD5 cause impairments in the PR-DUB complex that result in abnormal brain development, but critical insights in this area are currently lacking. My PhD project aims to fill this knowledge gap by characterising the function of MBD5 and determining its role in the PR-DUB complex during brain development. In silico expression analysis shows that MBD5 is ubiquitously expressed during organogenesis; but its levels are particularly high in post-mitotic neurons. Transcriptional analysis of in vitro derived neural cells supports these observations. Consistently, proteomic analysis confirmed that MBD5 expression is elevated on day-10 of neural differentiation. To determine its function, we are currently establishing transgenic mouse stem cell models that will be utilised with biochemical and genomic approaches. This will allow us to unravel the role of MBD5 during neurodevelopment and the mechanism underlying MAND.