ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3)

ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) is an endoplasmic reticulum-resident transmembrane protein that serves as a key negative regulator of de novo sphingolipid biosynthesis by mediating feedback inhibition of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in this metabolic pathway[6][1][5]. Overexpression or dysregulation of ORMDL3 has been strongly linked to asthma susceptibility, particularly in the airway epithelium, and is implicated in other inflammatory and autoimmune diseases including Crohn’s disease and type 1 diabetes[4][7]. Besides its primary role in lipid metabolism, ORMDL3 modulates immune responses by negatively regulating the type I interferon signaling pathway, impacting antiviral defense and anti-tumor immunity[2]. It also participates in regulating ER calcium homeostasis and the unfolded protein response, linking it to ER stress and related pathological conditions[7][4]. No approved drugs specifically target ORMDL3, but its key role in regulating both immune and metabolic pathways makes it of growing interest as a potential therapeutic target for asthma and other immunometabolic disorders.

Other names

ORMDL3Orosomucoid like 3Orosomucoid-like protein 3

Modulation of sphingolipid biosynthesis via feedback inhibition of serine palmitoyltransferase[6][5]. Alteration of immune cell function through negative regulation of interferon pathway signaling and calcium homeostasis[2][3][4].