CTD small phosphatase-like protein(CTDSPL) specially catalyzes the dephosphorylation of ’Ser-5’ within the tandem 7 residues repeats in the C-terminal domain(CTD) of the biggest RNA polymerase II subunit POLR2A. CTDSPL negatively regulates RNA polymerase II transcription, probably by directing the transition from initiation/capping to processive transcript elongation. CTDSPL is employed by REST to neuronal genes which contain RE-1 elements, directing to neuronal gene silencing in non-neuronal cells.