Recently, Habets et al. reported that the PS1 inhibitor MRK-560 effectively decreased mutant NOTCH1 processing in T cell acute lymphoblastic leukemia (T-ALL) cell lines, which were found to selectively express only PS1-containing γ-secretase complexes, suggesting that limiting side effects might be avoided by selective targeting of PS1 or PS2 [26]. Here, PSEN2 is linked to acute lymphoblastic leukemia.