RGPD4 (RANBP2 like and GRIP domain containing 4) is a nuclear protein involved in nucleocytoplasmic transport and SUMO-mediated signaling. Based on its domain architecture and GO annotations, RGPD4 participates in NLS-bearing protein import into the nucleus, nuclear export, and possesses SUMO transferase activity, suggesting roles in nuclear protein trafficking and post-translational modification [GO annotations]. Structurally, RGPD4 contains RANBP2-like and GRIP domains characteristic of nuclear pore complex-associated proteins. Clinically, RGPD4 mutations are associated with multiple disease contexts. In hepatocellular carcinoma (HCC), RGPD4 mutations correlate with increased vascular invasion risk in HBV-infected patients 1. RGPD4 carries de novo mutations in non-syndromic cleft lip/palate (NSCL/P) cases, with predicted high-confidence protein-protein interaction with SUMO1 (interaction score 0.868), consistent with its SUMO transferase function 2. In congenital pouch colon (CPC), RGPD4 is differentially expressed and associated with GTPase activator activity relevant to bowel development 3. Notably, RGPD4 harbors the densest human-specific islands of GGC trinucleotide repeats, suggesting evolutionary significance for human-specific characteristics including higher-order brain functions 4. These findings indicate RGPD4's multifaceted roles in nuclear transport, developmental processes, and disease pathogenesis across diverse organ systems.