FGFR2B is an epithelial-specific isoform of fibroblast growth factor receptor 2, generated by alternative splicing of the FGFR2 gene. It primarily binds to mesenchymal-derived FGF ligands (e.g., FGF7, FGF10) and plays critical roles in embryonic development, tissue repair, and epithelial homeostasis. In oncology, aberrant activation of FGFR2B—through overexpression, amplification, or ligand-dependent signaling—drives tumor progression in multiple cancers, particularly gastric, breast, and endometrial carcinomas. Its restricted expression pattern and ligand specificity make it a compelling therapeutic target, with inhibitors currently developed to block hyperactivated FGFR2B pathways in precision medicine.