ASAH2 (N-acylsphingosine amidohydrolase 2) is a neutral ceramidase functioning as a plasma membrane enzyme that hydrolyzes ceramides into sphingosine and free fatty acids at neutral pH 1. It catalyzes bidirectional reactions in sphingolipid metabolism, both degrading ceramides and synthesizing them from fatty acids and sphingosine, thereby regulating bioactive lipid signaling pathways controlling cell proliferation, apoptosis, and differentiation 1. ASAH2 participates in sphingomyelin degradation alongside sphingomyelinase to produce sphingosine-1-phosphate, including digestion of dietary sphingolipids 1. Disease relevance is substantial across multiple conditions. In cancer, β5-integrin upregulates ASAH2 through Src-STAT3 signaling to reduce ceramide levels and suppress chemotherapy-induced pyroptosis, conferring chemoresistance in lung and pancreatic cancers 2. ASAH2 protects myeloid-derived suppressor cells from ferroptosis by destabilizing p53, promoting tumor immune evasion 3. Conversely, genetic studies identify ASAH2 as protective against ovarian cancer risk 4. ASAH2 emerges as a potential early biomarker for Alzheimer's disease, with elevated serum levels preceding clinical symptoms 5. Clinically, ASAH2 inhibition represents a therapeutic strategy to reactivate pyroptosis in chemoresistant cancers and reduce MDSC-mediated immunosuppression. The enzyme's role in lipid homeostasis suggests broader applications in metabolic and neurodegenerative diseases 1.