CHST9 encodes a carbohydrate sulfotransferase that catalyzes the sulfation of chondroitin and dermatan sulfate, key components of proteoglycans and glycosaminoglycans involved in extracellular matrix structure and function. The enzyme adds sulfate groups to the C-4 position of β1,4-linked GalNAc residues 1, contributing to post-translational modifications of glycoproteins. Genetically, CHST9 variants associate with multiple disease and physiological states. GWAS meta-analysis identified CHST9 as one of five loci influencing circulating α-Klotho levels, a key regulator of phosphate homeostasis 2. The authors speculate that CHST9's post-translational modification function affects α-Klotho protein turnover and stability 2. CHST9 variants also associate with frailty risk in large-scale genome-wide studies, with colocalization analysis supporting a causal role 3, and with bronchopulmonary dysplasia susceptibility in premature infants, potentially through Wnt pathway interactions 4. In cancer contexts, CHST9 expression is downregulated in glioblastoma compared to non-GBM gliomas 5 and hepatocellular carcinoma 6, suggesting tumor-suppressive functions. Notably, CHST9 marks a distinct medium spiny neuron population in the nucleus accumbens with abundant opioid receptor expression across rodent, primate, and human species 78, implicating this population in opioid-related behaviors.