These changes may be a sign of lysosomal dysfunction, which might drive FTD-GRN pathogenesis by impairing neuronal autophagy and promoting TDP-43 aggregation [24] or by shifting microglia to a reactive phenotype that destroys synapses and promotes TDP-43 mislocalization in neurons [39, 42, 56, 94, 100]. The gene discussed is TARDBP; the disease is frontotemporal dementia.