Galactosylceramide 3-sulfotransferase (GAL3ST1) (GAL3ST1)

Galactosylceramide 3-sulfotransferase (GAL3ST1) is a Golgi-localized enzyme that catalyzes the transfer of a sulfate group from 3-phosphoadenosine-5-phosphosulfate (PAPS) to galactosylceramide to form sulfatide [1, 4]. Sulfatide is a major sphingolipid in the myelin sheath of the central and peripheral nervous systems, essential for maintaining the stability of myelin-axon interactions and the clustering of ion channels at the nodes of Ranvier [2]. In Metachromatic Leukodystrophy (MLD), a deficiency in the degradative enzyme arylsulfatase A causes toxic sulfatide accumulation, making GAL3ST1 a primary target for substrate reduction therapy (SRT) to limit sulfatide production [2, 4]. Beyond lysosomal storage disorders, GAL3ST1 is often overexpressed in various cancers, such as renal cell and colorectal carcinomas, where it contributes to tumor cell adhesion and metastatic potential [3]. It also plays a role in viral infections, as certain viruses like influenza A require sulfatides for efficient replication and host cell entry [3]. Currently, there are no FDA-approved drugs targeting GAL3ST1, but experimental approaches include small molecule inhibitors and mRNA-targeting antisense oligonucleotides [4]. Therapeutic challenges include the risk of demyelination if sulfatide levels are depleted below the threshold required for myelin maintenance [2].

Other names

Cerebroside sulfotransferaseCSTGalCer sulfotransferaseGAL3ST1Galactosylceramide 3-sulfotransferaseGalactosylceramide sulfotransferase mRNA

Substrate reduction therapy (SRT) via inhibition of sulfatide synthesis