Therefore, it is reasonable to speculate that under sustained calpain activation such as in ischemia, calpain-cleavage of fGAD65, not only liberated the functional moiety of the enzyme from the site of action at the SVs causing a sharp decline in the refilling kinetics, but also knocked down VGAT expression and activity, thereby collectively depleting the readily releasable pool of GABA loaded SVs, perturbing the already established functional coupling process from our previous work [17]. The gene discussed is SLC32A1; the disease is ischemia.