Human TFPI is a physiological inhibitor of the extrinsic pathway of coagulation and functions in anticoagulation and anti-inflammation. It is a secreted protein with an N-terminal acidic region, three Kunitz (K) domains separated by two linker regions, and a C-terminal basic region. The first K domain inhibits coagulation factor VIIa complexed to tissue factor (TF). The second K domain inhibits factor Xa. The third K domain binds to heparin. The C-terminal basic region may have several functions. Human TFPI-2 is structurally similar to TFPI and is downregulated in several cancers.