To elucidate the detailed molecular mechanisms underlying the distinct severity of skeletal dysplasias caused by two TRPV4 mutations (moderate brachyolmia-causing V620I vs. severe metatropic dysplasia-causing T89I), we used CRISPR-Cas9 gene editing to generate hiPSC-derived chondrocytes bearing either V620I or T89I mutation. Here, TRPV4 is linked to skeletal dysplasia.