RPRD1A is a nuclear protein that functions as a scaffold for RNA polymerase II (RNAPII) C-terminal domain (CTD) phosphorylation regulation. It forms homodimers and heterodimers through coiled-coil domains and interacts with RNAPII CTD repeats phosphorylated at S2 and S7, facilitating RPAP2-mediated dephosphorylation of phospho-S5 1. This interaction enables coordination of CTD modifications during transcription cycling. RPRD1A acts as a negative regulator of Wnt/β-catenin signaling by competitively binding β-catenin and disrupting TCF4-β-catenin transcription complex formation 2. It also stabilizes NRF2 through competitive interaction with TRIM21, enhancing oxidative stress defense in cells 3. In cancer contexts, RPRD1A expression is dysregulated: downregulated in breast cancer metastasis through miR-454-3p-mediated suppression, promoting Wnt signaling activation and metastatic progression 4; upregulated in hepatocellular carcinoma, aggravating disease progression through NRF2 stabilization 3; and targeted by miR-10a in acute myeloid leukemia, decreasing chemosensitivity via Wnt pathway activation 5. RPRD1A represents a potential biomarker and therapeutic target in multiple malignancies 6. Unlike its homolog CREPT/RPRD1B which promotes proliferation, RPRD1A inhibits cell proliferation 7.