Variants in BACE1 and/or γ-secretase substrates, as well as variants in PSEN1, encoding the catalytic domain of γ-secretase, are linked to many pathophysiological conditions, including Alzheimer’s disease, epileptic encephalopathy, cardiac disease, and cancer (26, 31, 44, 63–67). Here, BACE1 is linked to Alzheimer disease.