TAR-DNA-binding protein-43 (TDP-43) was identified as the major component of the proteinaceous inclusions present in ~97% ALS and ~45% frontotemporal dementia (FTD) patients, and has also been observed in an increasing spectrum of other neurodegenerative disorders, including Alzheimer disease. The gene discussed is TARDBP; the disease is early-onset autosomal dominant Alzheimer disease.