Progressive aggregation of TAR DNA-binding protein 43 (TDP-43) is a hallmark of numerous neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's disease, and limbic predominant age-related TDP-43 encephalopathy (LATE). The gene discussed is TARDBP; the disease is early-onset autosomal dominant Alzheimer disease.