The malignant character of high-grade gliomas and their PCD-resistance is closely linked to the severe activation of the TrkB receptor and its downstream PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, and PLCγ1/PKC pathways overexpression, which normally regulate neuronal and glial survival, proliferation, and differentiation but become dysregulated to sustain uncontrolled growth (Figure 1). The gene discussed is PRRT2; the disease is central nervous system cancer.