Messenger RNA differential display was applied to screen for the blood glucose regulated genes in SD rat skeletal muscle. The rat homologue of the mouse prominin was thus identified. Comparing to its mouse and human homologues, fudenine was C-terminal truncated due to a single nucleotide deletion. However, its mitochondrial energy transfer signature peptide PQDLVKKLI remained intact. Fudenine, an 592-amino acid containing, 66-kDa glycoprotein, is a novel plasma membrane protein with four transmembrane segments flanking by two large glycosylated extracellular domains. Although it is devoid of the last transmembrane domain comparing to its homologues, fudenine also locates in cell membrane by transfection of fusion plasmid pFudenine-EGFP into CBRH7919 cell and L-6TG: cell. Overexpression of fudenine in CBRH7919 cell line up-regulated the mRNA level of GAPDH (3-phosphate glyceraldehyde dehydrogenase), while long-term glucose exposure resulted to reduced GAPDH expression. Since high blood glucose level induced the expression of fudenine in skeletal muscle, which in turn up-regulated the expression of GAPDH, we propose that fudenine might be a candidate gene for diabetes mellitus.