CTDSPL2: A comprehensive review from molecular structure to clinical applications

C-terminal domain small phosphatase-like 2 (CTDSPL2), also known as SCP4, is a crucial member of the small C-terminal domain phosphatase (SCP/CTDSP) family. Recent studies have revealed that CTDSPL2 plays a pivotal role in cell cycle regulation, developmental processes, and tumorigenesis. This article systematically reviews the molecular structural characteristics, genetic localization, biological functions, and mechanisms of action of CTDSPL2 in various diseases. As a bifunctional phosphatase, CTDSPL2 not only participates in the transcriptional regulation of RNA polymerase II but also finely modulates the BMP/TGF-β signaling pathway and the epithelial-mesenchymal transition (EMT) process by dephosphorylating key signaling molecules such as Smad1/5/8 and Snail. In multiple cancers, CTDSPL2 exhibits tumor-suppressive properties, and its downregulation is closely associated with poor patient prognosis. Concurrently, CTDSPL2 also plays significant roles in erythrocyte differentiation, metabolic reprogramming, and epigenetic regulation. A deeper understanding of the multifunctional characteristics of CTDSPL2 will provide a theoretical foundation and experimental basis for developing novel targeted therapeutic strategies.