[The following essay is written by Jack C. Drda, MD/PhD University of Pittsburgh Medical Scientist Training Program: https://www.mdphd.pitt.edu/people/jack-drda. Jack C. Drda thanks Sander Houten, Associate Professor of Genetics and Genomic Sciences, Mt. Sinai for his critical review of portions of this essay.] Mevalonate Kinase Deficiency (MKD) is a rare medical condition where patients have fevers, joint pain, and inflammation. Since MKD patients can have these symptoms suddenly, MKD is defined as an “autoinflammatory” condition. (1) Genetic variants in the mevalonate kinase gene cause MKD. (2) Because of these variants, patients cannot effectively make important molecules called isoprenoids. These isoprenoid molecules are important in helping cells communicate with one another. Since MKD patients do not have enough isoprenoids, their cells communicate differently, activating inflammatory signals that are usually silenced. (3) These increased inflammatory signals are called cytokines, and its increase leads to the inflammation in MKD patients. (4) Many current treatments for MKD are called antibody therapies. These therapies bind to the cytokines, helping to prevent the “autoinflammation.” MKD is known to exist on a spectrum, with severe to more mild symptoms. (5) In the past, MKD was classified as either mild (Hyperimmunoglobulin D Syndrome, HIDS) or severe (Mevalonic Aciduria, MA). However, this naming system was dropped since it did not describe the underlying cause of the disease. (6) The gene that has these variants is called the MVK gene. The most common MVK variant is p.V377I, and MKD patient often are compound heterozygote for a more penetrant variant, such as p.H20P or p.I268T 5. More variants for the MVK are discovered every year as awareness of MKD increases and genetic testing becomes more widespread worldwide. Because of this increasing diversity in MKD, all the variants fall under the umbrella term of “Mevalonate Kinase Deficiency Spectrum Disorders.” On this spectrum, there can be “MKD-mild” or “MKD-severe.” At MKD and Me we represent and embrace this diversity with our logo. Its different colors represent the spectrum of this rare medical condition. Written by Jack Drda 1. Julie Krainer, Sandra Siebenhandl, and Andreas Weinhäusel, “Systemic Autoinflammatory Diseases,” Journal of Autoimmunity 109 (May 1, 2020): 102421, https://doi.org/10.1016/j.jaut.2020.102421. 2. Sander M. Houten et al., “Mutations in MVK, Encoding Mevalonate Kinase, Cause Hyperimmunoglobulinaemia D and Periodic Fever Syndrome,” Nature Genetics 22, (June 1999): 175–77, https://doi.org/10.1038/9691. 3. Murali K. Akula et al., “Control of the Innate Immune Response by the Mevalonate Pathway,” Nature Immunology 17, (August 2016): 922–29, https://doi.org/10.1038/ni.3487. 4. Maurizio Ceppi et al., “MicroRNA-155 Modulates the Interleukin-1 Signaling Pathway in Activated Human Monocyte-Derived Dendritic Cells,” Proceedings of the National Academy of Sciences 106, (February 24, 2009): 2735–40, https://doi.org/10.1073/pnas.0811073106. 5. Leslie A Favier and Grant S Schulert, “Mevalonate Kinase Deficiency: Current Perspectives,” The Application of Clinical Genetics 9, (July 20, 2016): 101–10, https://doi.org/10.2147/TACG.S93933. 6. Isabelle Touitou, “Twists and Turns of the Genetic Story of Mevalonate Kinase-Associated Diseases: A Review,” Genes & Diseases 9, (June 9, 2021): 1000–1007, https://doi.org/10.1016/j.gendis.2021.05.002.