2-hydroxyacylsphingosine 1-beta-galactosyltransferase (UGT8) (CGT)

Ceramide galactosyltransferase (CGT), also known as UGT8, is a key enzyme located in the endoplasmic reticulum that catalyzes the transfer of galactose from UDP-galactose to ceramide [1, 8, 14]. This reaction is the primary step in the biosynthesis of galactosylceramide (GalCer), which is a critical component of the myelin sheath in both the central and peripheral nervous systems [8, 15]. In the context of lysosomal storage diseases such as Krabbe disease and metachromatic leukodystrophy, CGT is a therapeutic target for substrate reduction therapy (SRT); by inhibiting this enzyme, researchers aim to limit the accumulation of toxic sphingolipids like psychosine and sulfatide [1, 2, 4]. Furthermore, UGT8 is overexpressed in aggressive cancers, particularly basal-like breast cancer, where it promotes tumor progression and metastasis by activating the sulfatide-integrin signaling axis [3, 8]. Pharmacological inhibition of CGT using small molecules like thienopyridines (e.g., RA 5557) or repurposed drugs like zoledronic acid is currently being explored as a strategy to treat these neurodegenerative and oncological conditions [2, 3, 4].

Other names

Ceramide galactosyltransferaseUDP-galactose:ceramide galactosyltransferaseGalactosylceramide synthaseCerebroside synthaseUGT8

Inhibition of ceramide galactosyltransferase to reduce the synthesis of galactosylceramide and its derivatives, thereby preventing the accumulation of toxic metabolites like psychosine in lysosomal storage disorders or pro-tumorigenic sulfatides in cancer.