Sphingosine-1-phosphate phosphatase 1 (SGPP1)

Sphingosine-1-phosphate phosphatase 1 (SGPP1) is an enzyme that specifically dephosphorylates sphingosine-1-phosphate (S1P), a bioactive signaling lipid, converting it back to sphingosine. This reaction is central to sphingolipid metabolism, facilitating recycling of sphingosine into long-chain ceramides. SGPP1 is mainly localized to the endoplasmic reticulum and regulates intracellular S1P levels, thereby modulating processes such as apoptosis (via ceramide synthesis), autophagy, cell migration, calcium signaling, and keratinocyte differentiation. Its dysregulation is implicated in skin diseases, cancer, inflammation, and vascular abnormalities[3][5][6]. Drugs that affect S1P signaling may indirectly impact SGPP1 function, but no direct SGPP1-targeted therapeutics are currently available.

Other names

SPP1SPPase1Sphingosine-1-phosphatase 1Sphingosine-1-phosphate phosphohydrolase 1hSPP1hSPPase1SPP-1spp1

Drugs targeting S1P metabolism generally modulate S1P levels, thereby affecting immune cell trafficking, angiogenesis, proliferation, and apoptosis[1][2]. For direct SGPP1 targeting, the expected mechanism would be inhibition or activation of S1P dephosphorylation, altering downstream sphingolipid signaling—however, no direct modulators are currently in clinical use or widely described[3].