 Introduction: Mevalonate Kinase Deficiency (MKD) is a periodic fever syndrome characterised by recurrent bouts of high fever and systemic inflammation. MKD is caused by recessive, hypomorphic mutations in the mevalonate kinase gene (MVK) encoding a key enzyme in the mevalonate pathway. This pathway is responsible for cholesterol synthesis and the production of isoprenoid lipid tags required for post-translational prenylation of proteins. It is believed that inflammation in MKD is triggered by shortage of isoprenoid lipids and defective prenylation of small GTPases. We have found that protein prenylation is indeed compromised in PBMCs from patients and this defect distinguishes MKD from other periodic fever syndromes. However, the link between protein prenylation and inflammation in MKD is still far from understood, largely due to the lack of suitable genetic mouse models.