RPRD1B (regulation of nuclear pre-mRNA domain containing 1B) is a transcriptional cofactor that plays critical roles in RNA polymerase II regulation and cell cycle control. The protein functions as a scaffold for RNA polymerase II C-terminal domain (CTD) dephosphorylation, forming homo- and heterodimers through coiled-coil domains and interacting preferentially with CTD repeats phosphorylated at serine 2 and 7 1. RPRD1B coordinates with RPAP2 phosphatase to facilitate serine 5 dephosphorylation of the CTD 1. The protein regulates 3' end processing of pre-mRNA through cleavage and polyadenylation, binding RNA and controlling RNA polymerase II release at gene termination sites 2. RPRD1B promotes cell proliferation by accelerating cell cycle progression through upregulation of cyclin D1, CDK4, and CDK6 3. In cancer contexts, RPRD1B is frequently overexpressed and correlates with poor prognosis across multiple cancer types including endometrial 3, cervical 4, gastric 5, and triple-negative breast cancers 6. The protein drives metastasis through transcriptional activation of oncogenic pathways, including the c-Jun/c-Fos/SREBP1 axis in gastric cancer 5 and formation of co-operational chr20 loops in triple-negative breast cancer 6. RPRD1B represents a potential therapeutic target, as its inhibition sensitizes cancer cells to treatment and suppresses metastasis in preclinical models 36.