In patient-derived chondrocytes, misfolded MMP13 protein upregulated HSPA5 expression, induced significant ER dilation, activated unfolded protein response and increased chondrocyte apoptosis, ultimately contributing to MMP13-related SS.<h4>Conclusion</h4>This study for the first time reports the MMP13 c.1372del (p.Arg458Valfs*31) variant causes autosomal dominant SS without obvious skeletal abnormalities. This evidence concerns the gene MMP13 and synovial sarcoma.