The here reported experimental evidence on the multiple effects exerted by PC-PLC inhibition on CXCR4 expression, signaling and cell metabolism in the human U87MG cells suggests that targeting the PC-PLC enzyme could represent a potential novel strategy for GBM treatment which could contribute to counteract tumor growth and progression by interacting with crucial components of glioma biology such as CXCR4 and EGFR receptors and their downstream effectors. The gene discussed is HSPG2; the disease is glioblastoma.