FGFR2 (fibroblast growth factor receptor 2) is a tyrosine kinase cell-surface receptor that plays critical roles in cell proliferation, differentiation, migration, and apoptosis regulation. The receptor functions through ligand-induced dimerization and autophosphorylation, activating downstream signaling cascades including MAPK and PI3K-AKT pathways 1. FGFR2 is essential for normal embryonic development, particularly in skeletal morphogenesis, and regulates epithelial cell-extracellular matrix interactions by controlling integrin β1 levels 2. In keratinocytes, FGFR2 suppresses inflammatory responses, with its downregulation contributing to atopic dermatitis pathogenesis 3. Clinically, FGFR2 alterations are significant oncogenic drivers, particularly FGFR2 fusions found in 10-15% of intrahepatic cholangiocarcinoma cases 4. These fusions represent actionable therapeutic targets, with FGFR inhibitors like pemigatinib showing objective response rates of 37% and median overall survival of 17.5 months in pretreated patients 5. However, acquired resistance commonly develops through secondary kinase domain mutations, particularly N550 and V565 mutations, occurring in 60% of treated patients 6. The receptor's phosphorylation is negatively regulated by PTPN9, which dephosphorylates FGFR2 at Y656/657 and synergistically enhances pemigatinib effectiveness 1.