MPV17 is a mitochondrial inner membrane protein that functions as a non-selective ion channel modulating mitochondrial membrane potential and maintaining mitochondrial homeostasis 1. The channel has a pore diameter of 1.8 nm with weak cation selectivity and voltage-dependent gating regulated by redox conditions and pH 1. Beyond channel function, MPV17 is critically involved in mitochondrial DNA (mtDNA) maintenance through regulation of mitochondrial deoxynucleoside triphosphate (dNTP) pool homeostasis, with evidence suggesting a role in pyrimidine de novo synthesis pathway 2. Loss of MPV17 function causes elevated mitochondrial membrane potential, increased reactive oxygen species production, and accelerated mitochondrial fission 1. Pathogenic MPV17 variants cause mitochondrial DNA depletion syndrome type 6 and Charcot-Marie-Tooth disease axonal type 2EE 3. MPV17 mutations are associated with hepatocerebral forms of mtDNA depletion syndromes, typically presenting with early-onset liver dysfunction and neurological involvement 4. In pediatric acute liver failure of indeterminate origin, MPV17 defects represent the second most frequent genetic finding after NBAS 5. Preliminary therapeutic approaches using pyrimidine supplementation show promise in restoring mtDNA content in MPV17-deficient models 2.