AOAH encodes acyloxyacyl hydrolase, a lipase that removes secondary fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (LPS), thereby inactivating the endotoxin and preventing prolonged inflammatory responses. Beyond LPS catabolism, AOAH also degrades oxidized phospholipids and regulates gut microbiota composition through LPS detoxification. AOAH is expressed in phagocytes, intestinal epithelium, liver, and proximal tubular epithelial cells, where it modulates multiple physiological processes. Genetic variants in AOAH are associated with asthma and elevated immunoglobulin E levels among African Caribbean populations 1, and AOAH polymorphisms have been replicated as risk factors for chr7 rhinosinusitis in both European and Chinese cohorts 23. AOAH-deficient mice exhibit dysbiosis, intestinal barrier dysfunction, and spontaneous pelvic pain with comorbid anxiety and depressive behaviors, phenotypes reversible by microbiota transfer or genetic rescue 45. In kidney disease, AOAH protects against fibrosis by inhibiting tubular CD74 signaling, and AOAH expression correlates positively with glomerular filtration rate in chr7 kidney disease patients 6. Recent evidence suggests AOAH potentiates immunotherapy responses in multiple tumor models by sensitizing T cell receptors and depleting immunosuppressive lipid mediators 7, and may prevent metabolic dysfunction-associated steatotic liver disease through intestinal LPS inactivation 8.