RHOT1 (ras homolog family member T1) is an atypical mitochondrial GTPase functioning as a master regulator of mitochondrial trafficking and dynamics. As an NTPase capable of hydrolyzing GTP, ATP, and UTP 1, RHOT1 controls anterograde mitochondrial transport and subcellular distribution 234. Mechanistically, RHOT1 recruits the trafficking adapter protein TRAK1 through multiple binding sites, enabling kinesin-1 and dynein-dynactin engagement for microtubule-based mitochondrial motility 5. During calcium stress, RHOT1 promotes mitochondrial fission 6 and contributes to mitochondrial-derived vesicle biogenesis for quality control 7. RHOT1 plays critical roles in intercellular mitochondrial transfer. Under hypoxia in hepatocellular carcinoma, HMGB1 upregulates RHOT1 expression, promoting mitochondrial transfer via tunneling nanotubes that enhances cancer cell invasiveness 8. Similarly, MIRO2-mediated mitochondrial transfer from cancer cells to fibroblasts drives pro-tumorigenic CAF differentiation 9. In bone immunity, osteocytes transfer mitochondria through RHOT1-dependent mechanisms to trigger STING-mediated antitumor responses against metastatic cancer 10. Clinically, RHOT1 dysfunction associates with type 2 diabetes; reduced RHOT1 expression in pancreatic β-cells impairs insulin secretion and mitochondrial function, with RHOT1 methylation predicting future T2D risk 11.