Human Acid Ceramidase, ASAH1 ELI

Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (PubMed: 10610716, PubMed: 7744740, PubMed: 15655246, PubMed: 11451951).

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: 10610716).

Has a higher catalytic efficiency towards C12-ceramides versus other ceramides (PubMed: 7744740, PubMed: 15655246).

Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (PubMed: 12764132, PubMed: 12815059).

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 (PubMed: 12764132).

Has also an N-acylethanolamine hydrolase activity (PubMed: 15655246).

By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes (PubMed: 17713573).

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 (PubMed: 22261821).

[Isoform 2]: May directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity.