Using hybrid mouse diversity panel, our laboratory uncovered a mitochondrial membrane protein TMEM11 as a regulator of Th1 cell effector function. My research focused on examining the role of TMEM11 in macrophages. Prior research has shown that the loss of PMI in Drosophila results in morphological changes in mitochondria causing changes in mitochondrial inner membrane cristae architecture and cellular respiration resulting in decreased ATP production. Using mouse primary bone marrow derived macrophages (BMDMs), we were able to demonstrate that the loss of TMEM11 does not affect the ability for macrophages to polarize and does not affect the expression of key mitochondrial membrane structural proteins including MIC60 and MIC10. Moreover, the loss of TMEM11 does not affect the expression levels of ETC complex proteins which is different from that observed in Drosophila. TLR stimulation-mediated cytokine response was normal in Tmem11-/- BMDMs. However, when infected with RNA viruses, vesicular stomatitis virus (VSV) and Influenza A virus (IAV), Tmem11-/- BMDMs showed reduced activation of the NLRP3 inflammasome, thereby less production of cytokines IL-1 and IL-18. Activation of the NLRP3 inflammasome ultimately leads to pyroptosis, which was reduced in Tmem11-/- BMDMs. Altogether, the loss of TMEM11 impairs activation of the NLRP3 inflammasome upon RNA virus infection.