[5][6][7][8] PGLYRP4 (formerly PGRP-Iβ), a member of a family of human Peptidoglycan Recognition Proteins (PGRPs), was discovered in 2001 by Roman Dziarski and coworkers who cloned and identified the genes for three human PGRPs, PGRP-L, PGRP-Iα, and PGRP-Iβ (named for long and intermediate size transcripts),[5] and established that human genome codes for a family of 4 PGRPs: PGRP-S (short PGRP or PGRP-S[9]) and PGRP-L, PGRP-Iα, and PGRP-Iβ.

[5][6] PGLYRP4 is constitutively expressed in the skin, in the eye, in the mucous membranes in the tongue, throat, and esophagus, in the salivary glands and mucus-secreting cells in the throat, and at a much lower level in the remaining parts of the intestinal tract.

[18][19] PGLYRP4 C-terminal PGRP domain contains central β-sheet composed of six β-strands surrounded by three α-helices and three short helices and N-terminal segment unique to PGRPs and not found in bacteriophage and prokaryotic amidases.

PGLYRP4 binds peptidoglycan, a polymer of β(1-4)-linked N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) cross-linked by short peptides, the main component of bacterial cell wall.

Thus, PGLYRP4 C-terminal PGRP domain has a preference for binding peptidoglycan fragments from Gram-positive cocci.

[21] The mechanism of bacterial killing by PGLYRP4 is based on induction of lethal envelope stress, which eventually leads to the shutdown of transcription and translation.

[21][22] PGLYRP4-induced oxidative and thiol stress involve malfunction of the respiratory electron transport chain in bacteria.

[28] Mouse PGLYRP4 plays a role in maintaining anti- and pro-inflammatory homeostasis in the intestine, skin, and lungs.

[30] PGLYRP4-deficient mice also have increased inflammatory responses in the lungs during S. pneumoniae-induced pneumonia associated with impaired bacterial clearance[28] and more severe pulmonary inflammation following Bordetella pertussis infection,[31] indicating anti-inflammatory role of PGLYRP4 in the lungs.