We established that RAPP is pathologically activated by signal sequence defects associated with a number of human diseases: aspartylglucosaminuria (aspartylglucosaminidase), Norrie disease (Norrie disease protein), hypoparathyroidism (parathyroid hormone), frontotemporal lobar degeneration (granulin), and many others (Pinarbasi et al., 2018; Karamysheva et al., 2019; Tikhonova et al., 2019; Karamyshev et al., 2020). Here, GRN is linked to frontotemporal dementia.