CHST5 (carbohydrate sulfotransferase 5) is a Golgi-localized sulfotransferase that catalyzes the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues on O-linked glycans 1. The enzyme preferentially sulfates core 2-based O-glycan structures but does not act on extended core 1 structures 1, and is involved in sulfation of endothelial mucins. CHST5 expression is regulated by dietary oligosaccharides and inflammatory signals in intestinal goblet cells. Treatment with galacto-oligosaccharides or 2'-fucosyllactose upregulates CHST5 expression 5-7 fold in LS174T goblet cells 23, while inflammatory cytokines IL-13, TNF-α, and bacterial flagellin also enhance CHST5 expression 4. CHST5 expression correlates with increased mucin sulfation and enhanced mucosal barrier function 5. Clinically, CHST5 dysfunction contributes to macular corneal dystrophy (MCD) development, as selective knockdown of Chst5 in mouse corneal endothelium induced experimental MCD with extracellular matrix impairments and corneal thinning similar to patients 6. Intracameral injection of wild-type Chst5 rescued corneal impairments in disease models 6, suggesting therapeutic potential for glycan-related disorders affecting barrier tissues.