Endoplasmic reticulum and Golgi ceramidase that catalyzes the hydrolysis of unsaturated long-chain C18:1-, C20:1- and C20:4-ceramides, dihydroceramides and phytoceramides into sphingoid bases like sphingosine and free fatty acids at alkaline pH (PubMed:26474409). 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:26474409). Controls the generation of sphingosine in erythrocytes, and thereby sphingosine-1-phosphate in plasma (By similarity). Through the regulation of ceramides and sphingosine-1-phosphate homeostasis in the brain may play a role in neurons survival and function (PubMed:26474409). By regulating the levels of pro-inflammatory ceramides in immune cells and tissues, may modulate the inflammatory response (PubMed:26938296). an N-acyl-(4R)-4-hydroxysphinganine + H2O = (4R)-hydroxysphinganine + a fatty acid H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sphing-4-enine = (5Z,8Z,11Z,14Z)-eicosatetraenoate + sphing-4-enine H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sphinganine = (5Z,8Z,11Z,14Z)-eicosatetraenoate + sphinganine H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-(4R)-hydroxysphinganine = (4R)-hydroxysphinganine + (5Z,8Z,11Z,14Z)-eicosatetraenoate H2O + N-(11Z-eicosenoyl)-sphing-4-enine = (11Z)-eicosenoate + sphing-4-enine H2O + N-(11Z-eicosenoyl)-sphinganine = (11Z)-eicosenoate + sphinganine H2O + N-(11Z-eicosenoyl)-(4R)-hydroxysphinganine = (11Z)-eicosenoate + (4R)-hydroxysphinganine H2O + N-(9Z-octadecenoyl)-sphing-4-enine = (9Z)-octadecenoate + sphing-4-enine H2O + N-(9Z-octadecenoyl)-sphinganine = (9Z)-octadecenoate + sphinganine H2O + N-(9Z-octadecenoyl)-(4R)-hydroxysphinganine = (4R)-hydroxysphinganine + (9Z)-octadecenoate an N-acylsphing-4-enine + H2O = a fatty acid + sphing-4-enine an N-acylsphinganine + H2O = a fatty acid + sphinganine Activated by Ca(2+) and inhibited by Zn(2+). Lipid metabolism; sphingolipid metabolism. Up-regulated with age in cerebeLlum and cerebrum. Down-regulated in immune cells and colonic epithelial cells by lipopolysaccharides/LPS. Homozygous knockout mice are viable and do not display overt phenotype with regard to fertility, body weight and anatomy (PubMed:26474409). They exhibit a decrease in ceramidase activity in brain, liver and lung tissues leading to the age-dependent accumulation of unsaturated long-chain C18:1-ceramides and the concomitant decrease in sphingosine and sphingosine-1-phosphate (PubMed:26474409). This is associated with a premature degeneration of Purkinje cells and age-dependent defects in motor coordination, skilled hindlimb function and balance capabilities (PubMed:26474409). Knockout mice also display exacerbated systemic inflammatory response (PubMed:26938296). Belongs to the alkaline ceramidase family.