Spondyloenchondrodysplasia with immune dysregulation (SPENCDI; MIM 607944) is an autosomal recessive disorder characterized by short stature, progressive metaphyseal irregularities, most often involving the long bones at the wrists and knees, which eventually resemble enchondromas, platyspondyly with vertebral endplate irregularities, intracranial calcifications and spasticity.  These skeletal findings are frequently associated with various autoimmune disorders or findings including systemic lupus erythematosus, Sjögrens’s syndrome, Raynaud’s disease, vitiligo, cytopenias, hemolytic anemia, hypothyroidism, pneumonia, recurrent fevers, arthritis/arthralgia and positive ANAs. SPENCDI is caused by loss of function mutations in the phosphatase, acid, type 5, tartrate-resistance gene (ACP5 or TRAP).  ACP5 regulates the activity of osteopontin via dephosphorylation.  Osteopontin is a molecule involved with bone reabsorption and immune regulation.