CHST6 encodes a sulfotransferase enzyme that catalyzes the transfer of sulfate groups to keratan sulfate proteoglycans, specifically targeting position 6 of N-acetylglucosamine residues 1. The enzyme is primarily expressed in corneal stromal keratocytes and plays a crucial role in keratan sulfate biosynthesis within the corneal stroma 1. CHST6 dysfunction leads to macular corneal dystrophy (MCD), an autosomal recessive disorder characterized by accumulation of unsulfated keratan sulfate proteoglycans forming abnormal deposits in the corneal stroma and endothelium 2. These deposits progressively impair corneal transparency and visual acuity 2. MCD exhibits significant genetic heterogeneity, with over 189 mutations identified worldwide, most being missense mutations clustered in functionally important protein regions 3. Different mutation types correlate with distinct immunophenotypes: truncation mutations cause severe phenotypes with complete loss of keratan sulfate expression, while missense mutations result in milder presentations 4. Recent research using patient-derived iPSCs reveals that CHST6 mutations also impair autophagy and mitochondrial function in corneal stromal cells, suggesting broader cellular dysfunction beyond keratan sulfate metabolism 5. Treatment currently relies on corneal transplantation, though emerging therapies targeting autophagy dysfunction show promise 5.