Spondyloenchondrodysplasia: an enigmatic immuno-osseus type I interferonopathy

Spondyloenchondrodysplasia (SPENCD) is a rare immuno-osseus disease due to biallelic mutations in ACP5, resulting in a loss of tartrate resistant acid phosphatase (TRAP) activity and enhanced type I interferon signalling. While TRAP was identified in the 1950s, ACP5 cloned in the 1990s, an Acp5 knock-out mouse reported in 1996, and more than 3000 articles are retrievable on PubMed using the terms ‘tartrate resistant acid phosphatase’ + ‘TRAP’, the immunopathology of SPENCD remains unclear. Here we describe the clinical phenotype and molecular architecture of SPENCD, review the biology of TRAP, and consider how TRAP deficiency leads to disturbed innate immunity.