CHST14 encodes carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (D4ST1), which catalyzes the transfer of sulfate to the C-4 hydroxyl of N-acetylgalactosamine residues in dermatan sulfate biosynthesis 1. The enzyme plays a critical role in forming 4-O-sulfated iduronic acid blocks in dermatan sulfate, preferentially modifying GalNAc residues in -IdoUA-GalNAc-IdoUA- sequences compared to -GlcUA-GalNAc-GlcUA- sequences 1. CHST14 is essential for proper collagen fibril assembly through dermatan sulfate-proteoglycan interactions, particularly involving decorin 2. Loss-of-function mutations in CHST14 cause musculocontractural Ehlers-Danlos syndrome (mcEDS-CHST14), a severe connective tissue disorder characterized by multiple congenital malformations, progressive skeletal deformities, skin hyperextensibility, and life-threatening complications including large subcutaneous hematomas 3. The deficiency results in negligible dermatan sulfate production and excessive chondroitin sulfate, leading to dispersed collagen fibrils and multisystem fragility 2. Studies using patient-derived iPSCs demonstrate impaired osteogenesis, providing insights into skeletal manifestations 4. CHST14 knockout mice exhibit perinatal lethality with placental vascular abnormalities, highlighting the enzyme's critical role in development 5.