Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH ( , ). 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 . Has a higher catalytic efficiency towards C12-ceramides versus other ceramides (, ). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (, ). For the reverse synthetic reaction, the natural sphingosine D-erythro isomer is more efficiently utilized as a substrate compared to D-erythro-dihydrosphingosine and D-erythro-phytosphingosine, while the fatty acids with chain lengths of 12 or 14 carbons are the most efficiently used . Has also an N-acylethanolamine hydrolase activity . By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes . Also indirectly regulates tumor necrosis factor/TNF-induced apoptosis (By similarity). By regulating the intracellular balance between ceramides and sphingosine, in adrenocortical cells, probably also acts as a regulator of steroidogenesis .
May directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity.
Subcellular locations: Lysosome, Secreted
Secretion is extremely low and localization to lysosomes is mannose-6-phosphate receptor-dependent.
Subcellular locations: Nucleus, Cytoplasm
A localization to the nucleus and the cytoplasm has also been reported for ASAH1, most probably for isoforms devoid of a signal peptide.
Broadly expressed with higher expression in heart.