Converts sphingomyelin to ceramide (PubMed:1840600, PubMed:18815062, PubMed:27659707, PubMed:25920558, PubMed:25339683, PubMed:33163980, PubMed:12563314). Exists as two enzymatic forms that arise from alternative trafficking of a single protein precursor, one that is targeted to the endolysosomal compartment, whereas the other is released extracellularly (PubMed:21098024, PubMed:9660788, PubMed:20807762). However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form (PubMed:20530211, PubMed:12563314, PubMed:20807762, PubMed:9393854, PubMed:22573858). In the lysosomes, converts sphingomyelin to ceramide (PubMed:20807762, PubMed:21098024). Plays an important role in the export of cholesterol from the intraendolysosomal membranes (PubMed:25339683). Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol (PubMed:25339683). Modulates stress-induced apoptosis through the production of ceramide (PubMed:8706124). When secreted, modulates cell signaling with its ability to reorganize the plasma membrane by converting sphingomyelin to ceramide (PubMed:12563314, PubMed:20807762, PubMed:17303575). Secreted form is increased in response to stress and inflammatory mediators such as IL1B, IFNG or TNF as well as upon infection with bacteria and viruses. Produces the release of ceramide in the outer leaflet of the plasma membrane playing a central role in host defense (PubMed:12563314, PubMed:20807762, PubMed:9393854). Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruginosa, induce apoptosis and regulate the cytokine response in infected cells (PubMed:12563314). In wounded cells, the lysosomal form is released extracellularly in the presence of Ca(2+) and promotes endocytosis and plasma membrane repair (PubMed:20530211). (Microbial infection) Secretion is activated by bacteria such as P. aeruginos, N. gonorrhoeae and others, this activation results in the release of ceramide in the outer leaflet of the plasma membrane which facilitates the infection. (Microbial infection) Secretion is activated by human coronaviruses SARS-CoV and SARS-CoV-2 as well as Zaire ebolavirus, this activation results in the release of ceramide in the outer leaflet of the plasma membrane which facilitates the infection. Lacks residues that bind the cofactor Zn(2+) and has no enzyme activity. Lacks residues that bind the cofactor Zn(2+) and has no enzyme activity. a sphingomyelin + H2O = an N-acylsphing-4-enine + H(+) + phosphocholine H2O + N-(octadecanoyl)-sphing-4-enine-1-phosphocholine = H(+) + N-octadecanoylsphing-4-enine + phosphocholine 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-dihexadecanoyl-sn-glycerol + H(+) + phosphocholine a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-sn-glycerol + H(+) + phosphocholine Binds 2 Zn(2+) ions per subunit (PubMed:27349982, PubMed:27725636). Hydrolysis of liposomal sphingomyelin is stimulated by incorporation of diacylglycerol (DAG), ceramide and free fatty acids into the liposomal membranes (PubMed:25339683). Phosphatidylcholine hydrolysis is inhibited by incorporation of cholesterol, ceramide, DAG, monoacylglycerol and fatty acids (PubMed:25339683). Antidepressants, namely amitriptyline, imipramine, desipramine, fluoxetine, sertraline, escitalopram, and maprotiline inhibit sphingomyelin phosphodiesterase activity (PubMed:33163980, PubMed:22573858). (Microbial infection) The secretory form is activated by P. aeruginosa, this activation results in the release of ceramide in the outer leaflet of the plasma membrane. (Microbial infection) The secretory form is activated by human coronavirus SARS-CoV-2, this activation results in the release of ceramide in the outer leaflet of the plasma membrane. Monomer. Interacts with SORT1; the interaction is required for SMPD1 targeting to lysosomes (PubMed:16787399). The secreted form is induced in a time- and dose-dependent by IL1B and TNF as well as stress and viral infection. This increase of the secreted form seems to be due to exocytosis of the lysosomal form and is Ca(2+)-dependent (PubMed:20807762, PubMed:22573858, PubMed:20530211). Secretion is dependent of phosphorylation at Ser-510 (PubMed:17303575). Secretion is induced by inflammatory mediators such as IL1B, IFNG or TNF as well as infection with bacteria and viruses (PubMed:12563314, PubMed:20807762). Proteolytically processed (PubMed:21098024, PubMed:9030779). Mature lysosomal form arises from C-terminal proteolytic processing of pro-sphingomyelin phosphodiesterase (PubMed:21098024). Both lysosomal and secreted forms are glycosylated but they show a differential pattern of glycosylation. Phosphorylated at Ser-510 by PRKCD upon stress stimuli. Phosphorylation is required for secretion. A common polymorphism arises from a variable number of hexanucleotide repeat sequence within the signal peptide region. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. There are two types of sphingomyelinases: ASM (acid), and NSM (neutral). Most abundant (90%). Intermediate abundance (10%). Low abundance (<1%). Belongs to the acid sphingomyelinase family. Variants Gln-294 and Val-485 have been originally reported as disease-causing mutations in NPDA and NPDB (PubMed:12369017, PubMed:15221801). These variants have been reclassified as benign polymorphisms (PubMed:23430512). Leiden Open Variation Database (LOVD)