NOD1 is an intracellular pattern-recognition receptor that detects bacterial peptidoglycans and initiates innate immune signaling. Functionally, NOD1 recognizes gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP) ligands 1 and activates NF-κB and inflammatory cytokine production through the RIPK2 pathway 2. NOD1 requires S-palmitoylation by the palmitoyltransferase ZDHHC5 for membrane recruitment to bacteria-containing endosomes, a critical step for immune signaling 1. Beyond bacterial sensing, NOD1 mediates endoplasmic reticulum stress-induced inflammation, linking innate immunity to ER dysfunction through the IRE1α/TRAF2 axis 3. Clinically, NOD1 has emerging roles in cancer and inflammation. Enterotoxigenic Bacteroides fragilis activates NOD1 to promote breast cancer stem cell properties and chemoresistance 4. In colorectal carcinoma, Fusobacterium nucleatum-induced neutrophil extracellular traps depend on NOD1/2 signaling 5, while in esophageal cancer, F. nucleatum directly activates the NOD1/RIPK2/NF-κB pathway 2. Conversely, NOD1 activation in tumor-associated macrophages enhances anti-PD-1 immunotherapy efficacy in hepatocellular carcinoma 6. NOD1 also regulates hematopoietic stem cell specification through Rho GTPase-dependent NF-κB activation 7 and drives osteolytic bone metastasis in KRAS-mutant lung cancer via the HOXC10/NOD1/ERK axis 8.