PGLYRP1 (peptidoglycan recognition protein 1) is a pattern recognition receptor central to innate immunity and immune regulation. Functionally, PGLYRP1 binds peptidoglycan motifs from Gram-positive bacteria, acting as both a bactericidal agent and intracellular sensor that recognizes the disaccharide GMTriP-K motif 1. Upon activation, PGLYRP1 complexes with NOD2 and GEF-H1 in macrophages to regulate antimicrobial gene expression 1, and interacts with TREM1 to promote cytotoxicity through the TREM1-Syk-Erk1/2-Stat3 axis 2. In cancer immunotherapy, PGLYRP1 presents paradoxical roles: it inhibits CD8+ T cell activation in tumors while simultaneously promoting myeloid cell-mediated immunosuppression in pancreatic cancer stem cells 34. PGLYRP1 deletion enhances antitumor immunity while protecting against autoimmune encephalomyelitis 3. In neuroinflammation, microglial PGLYRP1 upregulation potentiates reactive gliosis and behavioral changes 2. Clinically, salivary and gingival crevicular fluid PGLYRP1 levels correlate with periodontitis severity and inflammatory burden 56, serving as potential biomarkers for non-communicable diseases. PGLYRP1 represents a promising immunotherapeutic target with tissue-context-dependent functions requiring further investigation.