CTDSP2 (CTD small phosphatase 2) is a serine/threonine phosphatase that primarily functions in transcriptional regulation and cell cycle control 1. The protein preferentially dephosphorylates serine-5 residues within the C-terminal domain of RNA polymerase II, negatively regulating transcription by controlling the transition from initiation to elongation 1. CTDSP2 acts as a FOXO target gene that induces cell cycle arrest through its phosphatase activity, specifically by upregulating the CDK inhibitor p21 via Ras activation and both p53-dependent and p53-independent pathways 2. The protein demonstrates tumor suppressor properties in multiple cancer types. In clear cell renal cell carcinoma, lower CTDSP2 expression correlates with poor patient survival 3. Similarly, in non-small cell lung cancer, CTDSP2 shows frequent downregulation and functions as a tumor suppressor by dephosphorylating the Rb protein at multiple sites, thereby inhibiting cancer cell proliferation 4. CTDSP2 has also been identified as a potential driver gene in lung cancer through genome-wide screening 5. Additionally, the protein can functionally replace yeast phosphatases in TORC1 regulation under low leucine conditions, highlighting its evolutionary conservation 6.