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Target intelligence / Profile preview
Exostosin-like glycosyltransferase 2 (EXTL2)
- Target
- EXTL2
- Molecular classification
- Enzyme, Glycosyltransferase
01
Overview
Exostosin-like glycosyltransferase 2 (EXTL2) is a cytosolic and nuclear enzyme involved in the biosynthesis of heparan sulfate by catalyzing the incorporation of glucuronic acid and N-acetylglucosamine into glycosaminoglycan chains. It functions as a negative regulator of chondroitin sulfate proteoglycan synthesis, controlling extracellular matrix composition and inflammatory responses, particularly in neural injury settings such as demyelination. Genetic variants within the EXTL2 locus are significantly associated with susceptibility to multiple sclerosis, highlighting its role in neuroinflammatory disease. EXTL2 is classified as a glycosyltransferase but does not currently have known direct pharmacological inhibitors or modulators approved for clinical use.
- Other names
- Exostosin-like 2EXTR2Alpha-1,4-N-acetylhexosaminyltransferase EXTL2Alpha-GalNAcT EXTL2EXT-related protein 2Glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferaseProcessed exostosin-like 2Exostoses (multiple)-like 2
02
Biological functions
Biosynthesis of heparan sulfateCatalyzes alternating addition of beta-1,4-linked glucuronic acid and alpha-1,4-linked N-acetylglucosamine units to nascent heparan sulfate chainsLimits production of chondroitin sulfate proteoglycans (CSPGs) by terminating their synthesisInvolved in N-acetylglucosamine metabolic processInvolved in UDP-N-acetylgalactosamine metabolic process
03
Disease associations
Hereditary multiple exostosesBreast pericanalicular fibroadenomaMultiple sclerosis (genetic variants in EXTL2 recommended as a risk locus for MS)Neuroinflammation associated with demyelination injury
04
Safety considerations
Loss of EXTL2 leads to elevated deposition of CSPGs, which exacerbate axonal damage, impair remyelination, and increase neuroinflammation. These mechanisms suggest therapeutic modulation could present risks associated with CSPG accumulation and downstream effects on inflammation and neural tissue damage.
05
Biomarkers
Genetic SNPs in or around EXTL2 region serve as risk biomarkers for multiple sclerosis
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