We describe the isolation of a new gene that encodes a membrane-integrated protein with six transmembrane domains, termed TM6P1. A 403-bp expressed sequence tag was isolated from fasted rat liver subtracted cDNA library, and its full-length cDNA is 1482 bp long. It contains an open reading frame of 816 bp and is predicted to encode a 271-amino acid protein with a deduced mass of 29 520 Da. A sequence homology search failed to show significant correspondence to any known protein in the databank. TM6P1 has six highly hydrophobic domains that are predicted to be transmembrane helices. Consistent with this prediction, the TM6P1-EGFP fusion protein was shown to localize to the plasma membrane. TM6P1 mRNA is widely expressed in rat tissues, with placenta and liver being the most abundant sites. Fasting increased TM6P1 mRNA nearly two-fold in liver. Taken together, our data suggest that TM6P1 is a unique new membrane integral protein that might have a function important during fasting-induced catabolism.