Changes in the expression of the two principal inhibitors of cathepsin B, cystatin B and cystatin C, could also represent a redundant mechanism to prevent damage caused by free cathepsin B. However, an imbalance in the expression levels of these two proteins could lead to an increase in free active cathepsin B, which in turn could lead to neuronal dysfunction during HAND. This evidence concerns the gene CST3 and HIV-associated neurocognitive disorder.