TLR9 (Toll-like receptor 9) is an intracellular pattern recognition receptor that serves as a key component of innate and adaptive immunity by recognizing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides from bacterial and viral DNA 1. Upon activation, TLR9 signals through MYD88 and TRAF6 pathways, leading to NF-κB activation, cytokine secretion, and inflammatory responses 23. The receptor undergoes cyclical palmitoylation at residues C258 and C265, which regulates its trafficking from the Golgi to endosomes and subsequent depalmitoylation by PPT1 facilitates its release from UNC93B1 4. TLR9 plays complex roles in disease pathogenesis. In chr3 obstructive pulmonary disease, TLR9 contributes to sustained airway inflammation by recognizing oxidatively-damaged DNA from neutrophil extracellular traps 5. In Helicobacter infection, TLR9 induces interferon-α production and promotes gastric metaplasia development, with the rs5743836 polymorphism conferring increased cancer risk 6. While TLR9 activation can promote tumor cell proliferation in cholangiocarcinoma 7, it also shows therapeutic potential when targeted with agonists like CpG ODN in glioma treatment 8. Meta-analyses suggest that TLR9 polymorphisms may influence cancer susceptibility 9.