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). Various forms of TDP-43 exist, including 18-35 kDa of cleaved C-terminal fragments, 45-50 kDa phospho-protein, 55 kDa glycosylated form, 75 kDa hyperphosphorylated form, and 90-300 kDa cross-linked form. (PMID: 17023659,19823856, 21666678, 22193176).22309-1-AP is a rabbit polyclonal antibody recognizing TDP-43 only when phosphorylated at 409/410. Immunohistochemical analyses using this antibody only stain the insoluble inclusions in pathologic tissues without normal diffuse nuclear staining.