CANT1 (calcium-activated nucleotidase 1) is a calcium-dependent nucleotidase that preferentially hydrolyzes UDP, with lower activity against GDP, UTP, and GTP, and minimal activity toward ADP and ATP. It functions in proteoglycan synthesis, particularly in the production of dermatan and chondroitin sulfate chains attached to decorin, a proteoglycan critical for collagen fibril assembly in connective tissues including tendons and cartilage. Pathogenic CANT1 variants cause Desbuquois dysplasia, an autosomal recessive skeletal disorder characterized by multiple joint dislocations and developmental abnormalities. The phenotypic spectrum has expanded to include multiple epiphyseal dysplasia (MED), with patients carrying the same c.375G>C variant exhibiting features bridging both conditions 1. CANT1 dysfunction impairs dermatan/chondroitin sulfate synthesis, leading to defective decorin function and compromised collagen organization in the extracellular matrix 2. At the population level, gnomAD v4.1 classifies this gene as LoF-tolerant (LOEUF=1.24); however, 50 pathogenic or likely pathogenic ClinVar variants document clinical pathogenicity in skeletal dysplasias, distinct from population-level constraint. Recent evidence suggests CANT1 also functions as a cancer-associated gene. CANT1 is upregulated across multiple cancer types and correlates with poor prognosis in lung adenocarcinoma, hepatocellular carcinoma, and glioma 34. Mechanistically, CANT1 promotes lung cancer cell proliferation and invasion through NF-κB pathway activation 5. Genetic studies identify CANT1 as associated with scoliosis risk through methylation, immune, and metabolic pathways, suggesting multiple therapeutic avenues 6.