In a recent proteomic study of lysosomal proteins [10] we identified SID1 transmembrane family member 2 (Sidt2) as a novel lysosomal membrane protein candidate The Sidt2 gene encodes an 832-amino acid residues protein with a calculated molecular mass of 945 kDa Bioinformatic analysis showed that Sidt2 is a multipass transmembrane protein that contains 10 putative N-glycosylation sites (NxS/T) and two potential tyrosine-based sorting signals (YGSF and YDTL) Using specific anti-Sidt2 antibody and lysosomal markers the lysosomal localization of Sidt2 was determined by immunofluorescence Furthermore using subcellular fractionation techniques we demonstrated that Sidt2 is a lysosomal integral membrane protein Endogenous Sidt2 was detected in multiple tissues of mouse and rat with approximately 120-130 kDa molecular weights due to extensive glycosylation After digestion with PNGase F the apparent molecular mass of Sidt2 decreased to the predicted value of 95 kDa In rats Sidt2 was highly expressed in the liver brain and kidney whereas no or little expression was found in the skeletal muscles heart and other tissues In summary Sidt2 is a highly glycosylated lysosomal integral membrane protein that shows tissue-specific expression (C) 2010 Elsevier Inc All rights reserved