Using whole-cell patch-clamp recordings, we first confirmed that glutamatergic neurons expressing an ALS-causing variant of vapb (vapbP58S) or human tau (26, , –29) were constitutively depolarized relative to neurons expressing either GFP alone or wild-type vapb (vapbWT) (Fig. 2 D and E). Here, MAPT is linked to amyotrophic lateral sclerosis.