Human Far Upstream Binding Protein 1 (FUBP1) was discovered over 25 years ago, as a single stranded DNA binding protein and transcriptional activator of the MYC oncogene. The transcription factor MYC is upregulated in 70% of cancers and elevated MYC potently drives growth and proliferation. In accordance, FUBP1 is upregulated in many cancers, including breast, liver, bladder, kidney, lung and prostate. Moreover, our recent studies revealed that Psi, the Drosophila ortholog of FUBP1, interacts with the transcriptional Mediator (MED) complex to integrate developmental signals, activate MYC and promote cell and tissue growth in the wing epithelium. In contrast however, our recent unpublished data demonstrate expansion of the neuroblast stem cell lineage in the Drosophila brain after Psi depletion in stem cells and/or the stem cell niche comprising glial cells, suggesting anti-proliferative capacity in the context of neural lineages. In line with tissue-specific functions, FUBP1 knockout mice exhibit hypoproliferation in the embryonic blood lineage, while overgrowth occurs in the brain. Furthermore, in contrast to other tumour types, FUBP1 loss-of-function ranks in the top 10% of predicted driver mutations in oligodendroglioma, the second most common primary brain cancer in adults. The mechanisms behind these striking context-specific roles is unknown; therefore our current studies in Drosophila models focus on identification of key Psi transcriptional targets in both wing epithelium and neural stem cells.