Unexpectedly, genetic knockout of Nlgn3 gene from the cells in the microenvironment or pharmacological blockade via ADAM10 inhibition of Nlgn3 shedding in the brain microenvironment markedly slows glioma growth and progression in preclinical models of high-grade gliomas (adult glioblastoma, pediatric glioblastoma, diffuse intrinsic pontine glioma (DIPG)/DMG)2 and low-grade glioma (NF1-associated optic pathway glioma)3. Here, ADAM10 is linked to diffuse intrinsic pontine glioma.