Researchers investigated the role of LEDGF (encoded by the Psip1 gene) in the brain by creating mice with neuronal depletion of LEDGF. These mice showed motor deficits from a young age, along with changes in cerebellar neurons including altered MeCP2 organization and reduced expression of genes involved in synaptic transmission. Analysis of gene regulation networks pointed to an imbalance between the Trithorax complex (which LEDGF partners with via MLL1) and the Polycomb repressive complex 2, suggesting LEDGF normally helps maintain proper synaptic gene expression in the cerebellum. Because LEDGF interacts with POGZ — a protein central to White-Sutton syndrome — these findings may offer insights into the neurological features seen in affected individuals.