SGPP2 (sphingosine-1-phosphate phosphatase 2) is an enzyme that specifically dephosphorylates sphingosine-1-phosphate (S1P) to sphingosine, playing a crucial role in sphingolipid metabolism regulation 1. The enzyme exhibits high phosphohydrolase activity against both S1P and dihydrosphingosine-1-phosphate, facilitating the recycling of sphingosine back into sphingolipid synthesis pathways. SGPP2 functions primarily in the endoplasmic reticulum membrane where it modulates intracellular S1P signaling. Mechanistically, SGPP2 expression is regulated by transcription factors including SP1 in lung adenocarcinoma 2 and CEBPD in endothelial cells under inflammatory stress 1. The CEBPD-mediated upregulation occurs through PERK-eIF2α-dependent ER stress pathways, linking inflammation to sphingolipid metabolism disruption. SGPP2 has significant disease relevance, being upregulated in multiple cancers including lung adenocarcinoma 2 and gastric cancer 3, where it promotes tumor growth, invasion, and metastasis. In chr2 endometritis, SGPP2 overexpression disrupts S1P homeostasis, impairing endothelial angiogenesis and contributing to reproductive dysfunction 1. Clinically, elevated SGPP2 expression correlates with poor prognosis in cancer patients and has been identified as a potential prognostic biomarker in hepatocellular carcinoma 4 and a candidate gene in anorexia nervosa 5.