RHOT2 is an atypical mitochondrial nucleoside-triphosphatase (NTPase) that functions as a GTPase capable of hydrolyzing GTP, ATP, and UTP 1. Its primary role involves controlling anterograde mitochondrial transport and subcellular distribution along microtubules 2. Mechanistically, RHOT2 functions alongside DRP1 in mitochondrial-derived vesicle (MDV) biogenesis, where MIRO1/2-dependent membrane protrusions are formed and subsequently cleaved by DRP1 to generate MDVs enriched in phosphatidic acid 3. These MDVs deliver fully assembled protein complexes, including outer membrane β-barrel proteins and the TOM import machinery, to lysosomes for selective mitochondrial quality control 3. In neurons, RHOT2 dysfunction impairs mitophagy and triggers integrated stress response activation 4. Disease relevance includes Parkinson's disease, where RHOT2 variants were identified among 26 candidate genes in late-onset familial PD with disrupting mutations associated with increased disease risk 5, though large-scale consortium studies did not confirm RHOT2 as a disease-modifying locus 6. RHOT2 methylation patterns correlate with aging and appear as a potential biomarker for biological age decline 7. Clinically, RHOT2 silencing enhances colorectal cancer cell migration and invasion 8, and RHOT2 protein abundance associates with smoking initiation susceptibility 9.