To determine the target engagement and efficacy of S15JG, a mouse cross-reactive antibody that partly blocks the interaction of PGRN with sortilin and strongly decreases sortilin levels, WT and Grn+/− mice were used to model the PGRN haploinsufficiency that occurs in FTD-GRN [49]. The gene discussed is SORT1; the disease is frontotemporal dementia.