FGF16 (fibroblast growth factor 16) is a paracrine signaling protein that plays critical roles in cardiac development and stem cell proliferation. FGF16 belongs to the FGF9 subfamily and lacks an N-terminal signal peptide 1. The gene functions as a direct target of GATA4 transcription factor, with GATA4 binding to the FGF16 promoter to regulate its expression during cardiomyocyte development 2. FGF16 is essential for normal cardiomyocyte proliferation and heart development, as demonstrated by its ability to rescue proliferation defects in GATA4-mutant cardiomyocytes 2. The protein shows specific proliferative effects on cardiac progenitor cells while not affecting cardiac fibroblasts, suggesting receptor-specific mechanisms 3. Beyond cardiac function, FGF16 has diverse roles including inner ear development, where it defines spatial and temporal domains in the developing otic epithelium 4, and metabolic regulation in cancer cells through the PFKFB4-mediated glycolytic pathway 5. Loss-of-function mutations cause metacarpal 4-5 fusion in humans, highlighting its importance in limb development 6. DNA hypermethylation of FGF16 is associated with cleft palate formation 7. FGF16 represents a conserved WNT/β-catenin signaling target with potential therapeutic applications in cardiac regeneration 1.