Fibroblast growth factor (FGF)-9 and FGF-16 are rare secreted proteins that do not possess cleavable signal sequences. Inhibition of FGF-16 secretion from COS-1 transfectants by brefeldin A and identification of an N-glycan on the secreted form confirmed that FGF-16 is secreted via the endoplasmic reticulum and Golgi apparatus, like secreted proteins having a conventional cleavable signal sequence. Analysis of various mutants of FGF-9 and -16 have revealed that these proteins employ similar unique bipartite signal sequences Å| i.e., both the N-terminal region and central hydrophobic region Å| that is not cleaved, though it shares the same secretory machinery used by secreted proteins with cleavable signal sequences.