<p>Sphingomyelin phosphodiesterase, or sphingomyelinase (SMase), enzymes catalyse the hydrolysis of sphingomyelin into ceramide (N-acylsphingosine) and phosphorylcholine. There are six types of SMases: acid SMase, secretory SMase, neutral magnesium-dependent SMase, neutral magnesium-independent SMase, alkaline SMase, and bacterial SMase [<cite idref="PUB00014800"/>]. This entry covers the acid SMases.</p><p>Sphingomyelin is a ubiquitous lipid found in plasma membranes, as well in lipoproteins; in mammalian cells, it is the most abundant sphingolipid. Sphingoid molecules generated from the breakdown of sphingolipids can act as intracellular bio-modulators. In particular, ceramide can act as a second messenger in diverse signalling pathways leading to different cellular responses, such as apoptosis [<cite idref="PUB00014801"/>]. Hence, SMase activation can be an early event in the apoptosis-signalling cascade. SMase is regulated by several mechanisms, including tumour necrosis factor (TNF) receptor-associated protein FAN (Factor Associated with N-sphingomyelinase activation) and oxidative stress.</p>