CHST3 encodes chondroitin 6-O-sulfotransferase-1, a Golgi-resident sulfotransferase that catalyzes the transfer of sulfate to position 6 of N-acetylgalactosamine residues in chondroitin, the predominant proteoglycan in cartilage. The enzyme also acts with lower efficiency on keratan sulfate and sialyl N-acetyllactosamine oligosaccharides. Biallelic loss-of-function variants in CHST3 cause CHST3-related skeletal dysplasia, characterized by congenital joint dislocations (particularly at the knee and elbow), progressive vertebral anomalies, short stature, club feet, and cardiac valve abnormalities 12. The disorder displays substantial phenotypic variability; additional reported features include hearing loss, epiphyseal dysplasia, bifid humeri, and kyphoscoliosis 3. At the population level, gnomAD v4.1 classifies CHST3 as LoF-tolerant (LOEUF=1.12); this is distinct from clinical pathogenicity in skeletal dysplasia contexts, where 57 ClinVar pathogenic variants are documented. Recent evidence suggests CHST3 may also contribute to osteoporosis and sarcopenia pathogenesis as a differentially expressed gene 4. In cancer, upregulation of CHST3-dependent chondroitin sulfate promotes glioma cell migration and invasion via PI3K/AKT signaling 5.