TSC2 and neoplasm: Tuberous sclerosis complex is a genetic disease driven by hyperactivation of mTORC1, which is caused by loss-of-function mutations in TSC1 and TSC2. Given the accelerated G2/M checkpoint recovery in TSC2-depleted cells, we proposed a synthetic lethal approach that can selectively target TSC2-null tumor cells by ablating additional G2/M checkpoint signaling, thus inducing mitotic catastrophe.