Plasmanylethanolamine desaturase 1 (PEDS1) (TMEM189)

TMEM189, also known as Plasmanylethanolamine desaturase 1 (PEDS1), is an endoplasmic reticulum-resident enzyme that catalyzes the final and rate-limiting step in the biosynthesis of plasmalogens. It introduces a characteristic vinyl ether double bond into plasmanylethanolamine to produce plasmenylethanolamine, which is essential for maintaining membrane integrity and providing antioxidant protection against reactive oxygen species. In the context of oncology, TMEM189 is frequently overexpressed in various cancers, including breast cancer, where it acts as a ferroptosis inhibitor by maintaining plasmalogen levels, thereby promoting tumor cell survival and proliferation. Conversely, a deficiency in TMEM189 leads to a significant reduction in plasmalogens, a condition linked to neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as rare genetic disorders like rhizomelic chondrodysplasia punctata. Although no small molecule drugs targeting TMEM189 are currently approved for clinical use, it is considered a promising therapeutic target for inducing ferroptosis in therapy-resistant cancers and for restoring lipid homeostasis in metabolic and neurological conditions.

Other names

CARSKIAA0305PEDS1KuaCarF homologPlasmanylethanolamine Delta(1)-desaturaseCystine/Arginine-rich protein

Desaturation of the O-alkyl bond at the sn-1 position of ether lipids to form an O-alk-1-enyl (vinyl ether) bond.