FGF-4, also known as FGF-K or K-FGF (Kaposi’s sarcoma-associated FGF), is a 25kD secreted, heparin-binding member of the FGF family. The mouse FGF-4 cDNA encodes 202aa with a 29aa signal sequence and a 173aa mature protein with an FGF homology domain that contains a heparin binding region near the C-terminus. Mature mouse FGF-4 shares 87%, 90%, 87% and 85% aa identity with human, rat, canine and bovine FGF-4, respectively. Human FGF-4 has been shown to exhibit cross species activity. Expression of FGF-4 and its receptors, FGF R1c, 2c, 3c and 4, is spatially and temporally regulated during embryonic development. Its expression in the trophoblast inner cell mass promotes expression of FGF R2, and is required for maintenance of the trophectoderm and primitive endoderm. Later in development, FGF-4 works together with FGF-8 to mediate the activities of the apical ectodermal ridge, which direct the outgrowth and patterning of vertebrate limbs. FGF-4 is proposed to play a physiologically relevant role in human embryonic stem cell self-renewal. It promotes stem cell proliferation, but may also aid differentiation depending on context and concentration, and is often included in embryonic stem cell media in vitro. A C-terminally truncated 15kD isoform that opposes full-length FGF-4 and promotes differentiation is endogenously expressed in human embryonic stem cells. FGF-4 is mitogenic for fibroblasts and endothelial cells in vitro and has autocrine transforming potential. It is a potent angiogenesis promoter in vivo and has been investigated as therapy for coronary artery disease.