GPN1 (GPN-loop GTPase 1) is a small GTPase that plays a critical role in RNA polymerase II (RNAPII) nuclear import and assembly. The protein functions as a homodimer stabilized by its C-terminal tail, with the GTPase domain mediating dimer formation 1. GPN1 associates tightly with GPN3, another GTPase, and their protein levels are mutually dependent, suggesting they function as a heterodimeric complex 2. This complex directly interacts with RNAPII subunits, particularly RPB7/RPB4 and the C-terminal domain, facilitating nuclear import of the polymerase 3. Mechanistically, GPN1 shuttles between cytoplasm and nucleus, and its depletion leads to cytoplasmic accumulation of RNAPII and decreased nuclear levels 3. The protein exhibits GTPase activity that is essential for its function, as mutations in GTP-binding motifs impair RNAPII nuclear localization 4. GPN1 also associates with RPAP2, another RNAPII-associated protein involved in nucleocytoplasmic shuttling 5. In disease contexts, GPN1 shows increased expression in various cancers, particularly hepatocellular carcinoma, where it promotes cell migration and correlates with poor prognosis 6. Additionally, GPN1 expression is radiation-responsive, suggesting involvement in DNA damage responses 7.