The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. Monomer. Homodimer; disulfide-linked (By similarity). Membrane-associated in polymorphonuclear Leukocytes (PMN) granules. Expressed in testis, epididymis, and bone marrow, as well as in Sertoli and promyelocytic cell lines. Upon stimulation with different TLR ligands, it is strongly expressed in granulocytes and in bone marrow-derived dendritic cells. By lipopolysaccharide (LPS) through TRL4-TRIF-dependent pathway. Expression in Sertoli and promyelocytic cells is enhanced several-fold by all-trans retinoic acid. The N-terminal region may be exposed to the interior of the granule, whereas the C-terminal portion may be embedded in the membrane. During phagocytosis and degranulation, proteases may be released and activated and cleave BPI at the junction of the N- and C-terminal portions of the molecule, providing controlled release of the N-terminal antibacterial fragment when bacteria are ingested (By similarity). The N- and C-terminal barrels adopt an identical fold despite having only 13% of conserved residues. Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.