Researchers at Children’s Hospital of Philadelphia (CHOP) described a rare brain tumor case linked to adeno-associated virus (AAV) integration after intracisternal magna vector delivery for an inherited lysosomal disorder. The work, presented at ASGCT and published in the New England Journal of Medicine, documents a neuroepithelial tumor with PLAG1-driven biology. The patient received enzyme replacement therapy in infancy and a cord blood stem cell transplant before receiving AAV9-delivered iduronidase (IDUA) at 13 months of age. At age five, imaging identified an intraventricular mass that was surgically removed, and ongoing follow-up reported no tumor growth eight months post-resection. Tumor sequencing identified a fusion involving an AAV9 vector cassette fragment and PLAG1 exon 5 on chromosome 8, reinforcing concerns from preclinical work that integration events—while rare—can occur and may require enhanced long-term monitoring in gene therapy populations.