Sphingomyelin phosphodiesterase 3 (neutral sphingomyelinase 2) (SMPD3 (nSMase2))

Sphingomyelin phosphodiesterase 3 (SMPD3, also known as neutral sphingomyelinase 2 or nSMase2) is a membrane-associated hydrolase that catalyzes sphingomyelin hydrolysis to ceramide and phosphocholine. Ceramide serves as a critical second messenger in cellular processes including apoptosis, cell cycle regulation, response to stress, and exosome biogenesis. SMPD3 is predominantly expressed in the brain but also plays roles in other tissues including bones, vasculature, liver, and immune cells. Its dysregulation is associated with diseases such as neurodegeneration, inflammation, cancer, metabolic syndromes, and developmental disorders. SMPD3 is increasingly being investigated as a therapeutic target, with small-molecule inhibitors in preclinical development aimed at modulating ceramide-driven pathways. Regulation of SMPD3 is complex, involving transcriptional control, post-translational modifications, and subcellular localization, and therapeutic intervention requires careful consideration of its broad physiological impact

Other names

Neutral sphingomyelinase 2nSMase2Neutral sphingomyelinase IINSMASE2SMPD3Sphingomyelin phosphodiesterase 3NSMA2

Inhibition of ceramide generation (by blocking SMPD3's hydrolytic activity); Prevention of apoptosis- and inflammation-associated signaling; Inhibition of extracellular vesicle biogenesis; Modulation of neurodegenerative and inflammatory processes