Sphingolipids are hydrolyzed by ceramidases to yield sphingosine and fatty acids. These ceramidases are classified according to the pH range that supports their optimal activity. ASAH2 is a neutral ceramidase and key regulator of sphingolipid signaling metabolites at the cell surface, catalyzing the hydrolysis of the N-acyl linkage of ceramide at an optimal pH of 6.5-8.5. ASAH2 is a type II integral membrane protein that can be cleaved to yield a soluble secreted protein and acts as a repressor of apoptosis both by reducing C16-ceramide, thereby preventing ceramide-induced apoptosis, and generating sphingosine. Sphingosine exerts both mitogenic and apoptosis-inducing activities, and its phosphorylated form functions as an intra- and intercellular second messenger. ASAH2 is ubiquitously expressed primarily expressed with higher levels in the intestine, kidney, skeletal muscle and heart. Recent studies indicate that ASAH2 encoded neutral ceramidase is a key enzyme for the catabolism of dietary sphingolipids and regulates the levels of bioactive sphingolipid metabolites in the intestinal tract.