WWC2 (WW and C2 domain containing 2) functions as a critical regulator of the Hippo signaling pathway, acting as a tumor suppressor in multiple cancer types. The protein enhances phosphorylation of LATS1/2 kinases, which subsequently phosphorylates YAP, leading to its cytoplasmic retention and suppression of transcriptional activity 12. This mechanism negatively regulates cell proliferation and organ growth, making WWC2 an important guardian against tumorigenesis. In hepatocellular carcinoma, WWC2 expression is significantly downregulated and correlates with poor prognosis, advanced tumor features, and reduced overall survival 2. Similarly, in colorectal cancer, WWC2 mRNA stability is compromised through interaction with circXPO1 and FMRP, leading to Hippo-YAP pathway activation and enhanced tumor progression 3. Beyond cancer, WWC2 demonstrates tissue-specific functions, including regulation of GABA receptor trafficking in neurons 4 and high expression in testicular spermatocytes, potentially contributing to male fertility 5. The protein serves as a mediator in the CLK1-YAP cascade in intrahepatic cholangiocarcinoma development 6. Clinical significance includes its potential as a prognostic biomarker and therapeutic target across multiple malignancies.