Ranbp1, also known as HTF9A (Hpall Tiny Fragments Locus 9A), is a gene encoding a protein that plays regulatory functions in the RAN-network, belonging to the RAS superfamily of small GTPases. It regulates RANGAP1 activity and the balance between GTP-RAN and GDP-RAN, thus maintaining the nucleus-cytoplasmic gradient and enabling nuclear import-export. It is involved in the inter-nuclear transport of proteins, nucleic acids, and microRNAs, contributing to the cellular epigenomic signature. Ranbp1 is also implicated in spindle checkpoint formation, nucleation, and mitotic stability [1].

In mouse models, Ranbp1-/-embryos have facial phenotypes such as altered facial morphology and cleft palate, indicating it is a dosage-dependent modulator of craniofacial development. Its mutation disrupts BMP signaling-dependent midline gene expression and BMP-mediated craniofacial and cranial skeletal morphogenesis [2]. In addition, in high glucose-induced vascular smooth muscle cells, knockdown of NOTCH3, combined with overexpression of RanBP1, affects autophagy marker expression and cell viability, suggesting the RANBP1/NOTCH3 axis is crucial for autophagy and cell survival under hyperglycemic stress [3].

In conclusion, Ranbp1 is essential for multiple biological processes including nuclear-cytoplasmic transport, mitotic stability, and craniofacial development. Mouse models, especially the Ranbp1-/-model, have revealed its role in craniofacial dysmorphology related to 22q11.2 deletion syndrome and its function in autophagy regulation in high glucose-induced vascular smooth muscle cells, providing insights into potential disease mechanisms and therapeutic targets.