FRK (fyn-related kinase) is a non-receptor tyrosine kinase that functions primarily as a tumor suppressor through multiple mechanisms. FRK negatively regulates cell proliferation and stabilizes the PTEN phosphatase by phosphorylating it on tyrosine 336, preventing NEDD4-mediated degradation [UniProt]. In glioblastoma, FRK exerts tumor suppressive effects through distinct pathways: it inhibits JNK/c-Jun signaling to reduce migration and invasion 1, promotes N-cadherin/β-catenin complex formation at the plasma membrane to suppress glioma cell motility 2, and phosphorylates YAP (Yes-associated protein) on tyrosines 391/407/444, recruiting the E3 ubiquitin ligase Siah1 to mediate YAP degradation 3. However, FRK exhibits tissue-specific functional heterogeneity, displaying oncogenic properties in pancreatic and liver cancers where FRK knockdown suppresses proliferation 4. In hepatocellular adenomas, FRK mutations associate with specific tumor subtypes 5. This context-dependent duality—tumor-suppressive in glioma and breast cancer but potentially oncogenic in other tissues—highlights the importance of tissue-specific investigation when considering FRK as a therapeutic target.