[5][6][7][8] PGLYRP3 (formerly PGRP-Iα), 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] PGLYRP3 is constitutively expressed in the skin, in the eye, and in the mucous membranes in the tongue, throat, and esophagus, and at a much lower level in the remaining parts of the intestinal tract.

[17] PGLYRP3 C-terminal PGRP domain contains a central β-sheet composed of five β-strands and three α-helices and N-terminal segment unique to PGRPs and not found in bacteriophage and prokaryotic amidases.

[16] Human PGLYRP3 C-terminal PGRP domain, similar to PGLYRP1,[17] has three pairs of cysteines, which form three disulfide bonds at positions 178–300, 194–238, and 214–220.

PGLYRP3 C-terminal PGRP domain contains peptidoglycan-binding site, which is a long cleft whose walls are formed by α-helix and five β-loops and the floor by a β-sheet.

[18] Located opposite the peptidoglycan-binding cleft is a large hydrophobic groove, formed by residues 177–198 (the PGRP-specific segment).

PGLYRP3 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.

[6][23][24][25] The mechanism of bacterial killing by PGLYRP3 is based on induction of lethal envelope stress, which eventually leads to the shutdown of transcription and translation.

[11][28][29] Mouse PGLYRP3 plays a role in maintaining anti- and pro-inflammatory homeostasis in the intestine and skin.