People with Down syndrome (DS) (trisomy 21) have impaired immune function making them susceptible to infections and autoimmune disease. The molecular cause for this impairment is undetermined. Using mice we have found that an excess of RCAN1, a protein expressed at higher than normal levels in DS, adversely affects key immune functions, and that an excess of RCAN1 leads to suppression of the immune system. Our findings are of clinical relevance to DS and may also find application in situations in the non-DS population where suppression of the immune system is desirable; for example, in autoimmune disease or graft versus host responses. (By Dr. Melanie Pritchard, http://jmg.bmj.com/content/early/2013/05/02/jmedgenet-2013-101522 )