Transactivation response (TAR) DNA-binding protein of 43 kDa (also known as TARDBP or TDP-43) was first isolated as a transcriptional inactivator binding to the TAR DNA element of the HIV-1 virus. Neumann et al. (2006) found that a hyperphosphorylated, ubiquitinated, and cleaved form of TARDBP, known as pathologic TDP-43, is the major component of the tau-negative and ubiquitin-positive inclusions that characterize amyotrophic lateral sclerosis (ALS) and the most common pathological subtype of frontotemporal lobar degeneration (FTLD-U). This antibody recognizes the cleavage product of 20-30 kDa in addition to the native and phosphorylated forms of TDP-43. Immunohistochemical analyses of TDP-43 using this antibody detect both normal diffuse nuclear staining and insoluble inclusions in pathologic tissues.