Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:11328816, PubMed:10488143, PubMed:15217782). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:11328816). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (PubMed:15123644, PubMed:11278489). Together with sphingomyelinase, participates in the production of sphingosine and sphingosine-1-phosphate from the degradation of sphingomyelin, a sphingolipid enriched in the plasma membrane of cells (PubMed:15217782). Also participates in the hydrolysis of ceramides from the extracellular milieu allowing the production of sphingosine-1-phosphate inside and outside cells. This is the case for instance with the digestion of dietary sphingolipids in the intestinal tract (By similarity). an N-acylsphing-4-enine + H2O = a fatty acid + sphing-4-enine H2O + N-hexadecanoylsphing-4-enine = hexadecanoate + sphing-4-enine H2O + N-tetradecanoylsphing-4-enine = sphing-4-enine + tetradecanoate H2O + N-(9Z-octadecenoyl)-sphing-4-enine = (9Z)-octadecenoate + sphing-4-enine H2O + N-(15Z-tetracosenoyl)-sphing-4-enine = (15Z)-tetracosenoate + sphing-4-enine H2O + N-octanoylsphing-4-enine = octanoate + sphing-4-enine H2O + N-dodecanoylsphing-4-enine = dodecanoate + sphing-4-enine H2O + N-(hexanoyl)sphing-4-enine = hexanoate + sphing-4-enine H2O + N-octadecanoylsphing-4-enine = octadecanoate + sphing-4-enine hexadecanoate + sphinganine = H2O + N-hexadecanoylsphinganine H2O + N-(octadecanoyl)-sphinganine = octadecanoate + sphinganine Binds 1 zinc ion per subunit. The reverse reaction is inhibited by Zn(2+) and Cu(2+) (PubMed:11278489). Inhibited by cardiolipin and phosphatidic acid (PubMed:11278489). More efficiently hydrolyzes N-lauroylsphingosine/C12:0-ceramides compared to N-palmitoylsphingosine/C16:0-ceramides and N-stearoylsphingosine/C18:0-ceramides (PubMed:11328816). The catalytic efficiency towards dihydroceramides and phytoceramides is very low (PubMed:11328816, PubMed:10488143). For the reverse synthetic reaction exhibits a higher activity with D-erythro-sphing-4-enine and the fatty acid tetradecanoate as substrates (PubMed:11278489). Optimum pH is 6-7 for N-hexadecanoylsphing-4-enine hydrolysis (PubMed:11328816). Optimum pH is 7-10 for N-hexadecanoylsphing-4-enine hydrolysis (PubMed:10488143). Optimum pH is 6-8 for N-(octanoyl)-sphing-4-enine hydrolysis (PubMed:15217782). Optimum pH is 6.5-7 for hexadecanoate in the reverse reaction (PubMed:11278489). Lipid metabolism; sphingolipid metabolism. Enriched in exosomes upon stimulation by cytokine (By similarity). Enriched in caveolae and lipid rafts (By similarity). The localization to the mitochondrion could not be confirmed (By similarity). Highly expressed in brain, kidney and heart (PubMed:11328816). Expressed at lower level in other tissues such as liver (PubMed:11328816). Expressed in intestine, kidney and liver (at protein level) (PubMed:11328816, PubMed:11330410). Localizes in the epithelia of the jejunum and ileum (PubMed:11330410). By interleukin-1-beta in renal mesangial cells. Proteolytic cleavage of the N-terminus removes the signal-anchor and produces a soluble form of the protein. N-glycosylated (PubMed:11328816, PubMed:15123644). Required for enzyme activity (PubMed:11328816). O-glycosylated (PubMed:12499379). Required to retain it as a type II membrane protein at the cell surface (PubMed:12499379). Phosphorylated. May prevent ubiquitination and subsequent degradation. Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by nitric oxide. Belongs to the neutral ceramidase family.