Spondylocheirodysplastic Ehlers-Danlos syndrome (SCD-EDS) and the mutant zinc transporter ZIP13

The zinc transporter protein ZIP13 plays crucial roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). We recently reported that the pathogenic mutations in ZIP13 reduce its functional protein level by accelerating the protein degradation via the VCP-linked ubiquitin proteasome pathway, resulting in the disturbance of intracellular zinc homeostasis that appears to contribute to SCD-EDS pathogenesis. Finally, we implicate that possible therapeutic approaches for SCD-EDS would be based on regulating the degradation of the pathogenic mutant ZIP13 proteins.