ORMDL sphingolipid biosynthesis regulator 2 (ORMDL2)

ORMDL sphingolipid biosynthesis regulator 2 (ORMDL2) is a small transmembrane protein located in the endoplasmic reticulum, part of the ORMDL family (including ORMDL1 and ORMDL3) that regulates cellular sphingolipid levels by inhibiting the activity of serine palmitoyltransferase (SPT) in response to increased ceramide concentrations[1][3][8]. This negative feedback ensures homeostasis of sphingolipid metabolism and prevents accumulation of toxic intermediates that can impair processes such as myelination and immune cell function[3][5]. ORMDL2 is not a classic therapeutic target (e.g., receptor or enzyme), but loss or dysregulation can contribute to disorders involving sphingolipid metabolism such as neurodegeneration and inflammation[1][3][5]. Although some studies suggest potential disease associations, currently no drugs are reported to directly target ORMDL2.

Other names

ORM1-like protein 2HSPC160MSTP095MST095adoplin-20610012C09RikORM1-like 2 (S. cerevisiae)

Feedback inhibition of serine palmitoyltransferase (SPT) activity by sensing ceramide levels