Xbp1s mRNA has been identified in the ‘disease signature’ of many conditions resulting from the ER retention of misfolded mutant protein [34] and in particular several diseases characterised by the formation of insoluble intracellular aggregates such as type II diabetes [20], Alzheimer’s disease [17, 35], Huntington’s disease [18, 19], metaphyseal chondrodysplasia type Schmidt (MCDS) [6, 36] and matrilin-3 related multiple epiphyseal dysplasia (EDM5) [5, 33], suggesting XBP1-dependent modulation of ER stress in these conditions. The gene discussed is MATN3; the disease is multiple epiphyseal dysplasia.