High-grade gliomas (HGG) such as glioblastoma (GBM) and diffuse midline glioma (DMG) are extremely aggressive brain cancers with poor patient prognoses. Little improvement has been made to the treatment of these cancers over the last four decades, resulting in a push toward finding novel treatment targets. This study intends to explore ErbB4, a cell surface transducer with a potential link to the progression of high-grade gliomas. Increased ErbB4 activation in glioblastoma cells has been associated with increased tumorigenicity, proliferation, and angiogenesis in xenograft models. Furthermore, increased activation of ErbB4 in patient samples is associated with shorter patient survival. However, the molecular mechanisms behind these associations are not yet known. Understanding ErbB4 and its function in HGG could elucidate a role for it as a viable target for the treatment of the aforementioned cancers. The role of ErbB4 in GBM and DMG will be investigated using patient-derived cell lines for these cancers that closely mimic clinical pathology. So far, ErbB4 expression patterns in these cell lines were investigated via RT-qPCR and western blot, showing that there is high expression of ErbB4 mRNA and protein in HGG patient cell lines. Interestingly, the JM-a-CYT-2 isoform of ErbB4 was predominant in HGG, which is abnormal for brain tissue. This isoform has displayed properties such as ligand-independent autophosphorylation that may cause it to be oncogenic. In further study, previously optimised CRISPR and shRNA methods will be used to knock ErbB4 out/down in GBM and DMG cell lines. In vitro and in vivo experiments will then be conducted to compare ErbB4-deficient cell lines against the ErbB4-expressing parental cell lines to determine the effect that ErbB4 is having on the metastatic phenotype and its viability as a therapeutic or prognostic marker.