TAR DNA-binding protein is a cellular factor of 43 kDa that binds specifically to pyrimidine-rich motifs in TAR. Antibody to TDP-43 was used in gel retardation assays to demonstrate that endogenous TDP-43, present in HeLa nuclear extract, also bound to TAR DNA.

Although TDP-43 bound strongly to double-stranded TAR DNA via its ribonucleoprotein protein- binding motifs, it did not bind to TAR RNA extending from 1 to 80. TDP-43 is capable of modulating both in vitro and in vivo HIV-1 gene expression by either altering or blocking the assembly of transcription complexes that are capable of responding to Tat.TDP-43 is the major disease protein in both disorders.