TLR9 is a 145-150kD member of the Toll-like receptor family of molecules. It is expressed by colonic epithelium, CD123+ plasmacytoid dendritic cells, and transitional B cells, and responds to unmethylated DNA CpG motifs that exhibit either a GTCGTT sequence (in human), or a GACGTT sequence (in mouse). TLR9 is found in the ER, and translocates to either the cell membrane, or to lysosomes where it binds bacterial DNA. Precursor human TLR9 is a type I transmembrane protein 1032aa in length. It possesses a 793aa extracellular region that contains 26 LRRs (aa26-818), plus a 193aa cytoplasmic domain. The full-length 150kD form is suggested to be ligand-binding but nonsignaling. The active form is believed to be an 80kD cleavage product found in the endosome compartment. There are multiple splice forms. One contains a deletion of aa2-16, a second possesses an alternate start site at aa58, while a third and fourth show alternative start sites aa23 and 24 upstream of the standard site. Over aa64-189, human TLR9 shares 76aa identity with mouse TLR9.