RPAIN (RPA interacting protein) serves multiple cellular functions, with its primary role being the mediation of RPA complex nuclear import, potentially through interactions with importin beta, and sumoylation-dependent localization of RPA complex to PML nuclear bodies for DNA metabolism functions. Recent research has identified significant disease associations for RPAIN. Genetic variants in RPAIN, particularly rs8070740, are associated with increased susceptibility to influenza A H1N1 infection, with the G allele conferring up to 3.3-fold increased risk 1. RPAIN variants have also been linked to HIV infection susceptibility, where upregulation may contribute to disease progression 2. In Alzheimer's disease, RPAIN is among five genes showing significant dysregulation in blood-based transcriptome analysis 3. Additionally, a long non-coding RNA variant of RPAIN (NR_027683.1) is significantly upregulated in early-onset preeclamptic placentas and functions as a pathogenic regulator by inhibiting trophoblast invasion and promoting apoptosis through downregulation of complement protein C1q 4. The gene has also emerged as a candidate disease gene through genotype-phenotype matching approaches 5. These findings suggest RPAIN plays critical roles in immune responses and cellular regulation, making it a potential therapeutic target for multiple conditions.