The fact that caspase-1 and caspase-11 can be upstream of caspase-3 is supported by observations that caspase-1 initiates apoptosis in the absence of GSDMD [71], that caspase-1, independent of caspase-8, activates caspase-3 and caspase-7, leading to apoptotic features of pyroptosis [72], that caspase-11 is a critical initiator for caspase-3 in a mouse stroke model [73], and that loss of Casp1 and Casp11 prevents caspase-3 activation in epidermis in cpdm mice [37]. The gene discussed is CASP1; the disease is Stroke.