The recent identification of CLIC1 outside the cellular environment, in biological fluids like plasma [21] and serum [22, 23], urine [24] and in the medium of different cell lines often in association with secreted EVs [25–31], fostered the hypothesis that a circulating CLIC1 protein is detectable in the context of brain tumors in association to EVs, and it might potentiate the function of CLIC1 intracellular reservoir as a novel regulator of GBM growth. The gene discussed is CLIC1; the disease is brain neoplasm.