N-acylsphingosine amidohydrolase 2 (ASAH2)

N-acylsphingosine amidohydrolase 2 (ASAH2), commonly called neutral ceramidase, is a membrane-associated hydrolase that catalyzes the breakdown of ceramide into sphingosine and fatty acids at neutral pH. Ceramide, sphingosine, and sphingosine-1-phosphate are bioactive lipids involved in fundamental cellular signaling pathways controlling cell proliferation, differentiation, and apoptosis. ASAH2 is predominantly expressed in the small intestine, kidney, liver, and colon, and is essential for dietary sphingolipid digestion and regulation of cellular homeostasis. Its subcellular localization includes the plasma membrane, mitochondria, Golgi, and endosomes. Neutral ceramidase has structural features comprising a Zn-dependent catalytic domain and an immunoglobulin-like domain. Dysregulation or genetic variation of ASAH2 is implicated in cancer (especially colorectal), lipid-storage disorders such as sphingolipidosis, and various inflammatory or neurodegenerative processes. Targeting ASAH2 for therapeutic intervention is being actively investigated, although approved drugs specifically against ASAH2 are not yet available.

Other names

Neutral ceramidaseNon-lysosomal ceramidaseASAH2HNAC1N-CDaseNCDasehCDAcylsphingosine deacylase 2BCDaseLCDasemitochondrial ceramidaseneutral/alkaline ceramidase

Enzyme inhibition (blocking ceramide breakdown, leads to accumulation of ceramide, impacting cell signaling) Modulation of sphingolipid signaling pathway (altering balance between ceramide, sphingosine, and sphingosine-1-phosphate)