GTPBP8 (GTP binding protein 8) is a mitochondrial GTPase that serves as a critical regulator of mitochondrial biogenesis and dynamics. Functionally, GTPBP8 acts as the human homolog of bacterial EngB and plays a central role in mitoribosome large subunit assembly 1. The protein functions as an RNA-binding factor that directly interacts with mitochondrial 16S rRNA, facilitating proper maturation of large subunit assembly intermediates 1. Additionally, GTPBP8 modulates mitochondrial fission through a Drp1-dependent mechanism, with depletion causing mitochondrial elongation and interconnectedness, while overexpression promotes fragmentation 2. Mechanistically, GTPBP8 ablation impairs mitochondrial translation and oxidative phosphorylation capacity 1, while GTPBP8 overexpression activates Drp1 recruitment to mitochondria and enhances fission 2. The protein interacts with PGC-1α, a master regulator of mitochondrial biogenesis, linking GTPBP8 to transcriptional control of mitochondrial function 3. Clinically, GTPBP8 deficiency exacerbates nonalcoholic steatohepatitis (NASH) progression, with hepatocyte-specific knockout mice showing accelerated lipid accumulation, inflammation, fibrosis, and reactive oxygen species production 3. GTPBP8 overexpression in hepatocytes attenuates NASH phenotypes by reducing oxidative stress and mitochondrial dysfunction via PGC-1α signaling 3. These findings suggest targeting the GTPBP8/PGC-1α axis represents a potential therapeutic strategy for NASH treatment.