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Glioma progression is associated with up-regulation of the lysosomal cysteine proteases cathepsins B and L, which take part in various cellular processes.These include partial or extensive degradation of protein substrates, recycling of relevant biological molecules, such as receptors and growth factors and post-translational modifications of intracellular and secretory proteins.A broad pH optima and selective specificity of these enzymes, which activity is tuned by at least three cystatins (stefins A and B and cystatin C), allow them to participate in critical processes relevant for intracranial tumour progression, such as apoptosis, angiogenesis, invasion and drug resistance.Recent experiments using various methods for knocking out and silencing cathepsin genes in glioblastoma cells have clearly revealed differential expression and interesting functions of these enzymes.These may also effect gene regulation in the same and/or surrounding cells, indicating on an interesting effects of tumour microenvirortment on glioblastoma proliferation and invasion.A review of recent experimental and clinical findings in glioma will be presented and discussed.