Amplified in Osteosarcoma 9 (OS-9) was identified as a gene that is frequently amplified in human sarcomas (1). OS-9 is an N-glycosylated ER resident protein that harbors a mannose-6-phosphate receptor homology (MRH) domain and plays a critical role in mammalian ER quality control, in part, by functioning as a lectin. There are two major isoforms of OS-9 (OS-9-1, OS-9-2) that are generated through alternative splicing of mRNA (2). The expression of both OS-9 isoforms is enhanced upon activation of the IRE1/XBP1 pathway in cells exposed to acute ER stress. It is postulated that OS-9 serves as a retention factor for glycosylated and nonglycosylated, misfolded proteins, preventing their progression through the secretory pathway (3,4). Furthermore, OS-9 promotes the removal of misfolded proteins from the ER lumen and their subsequent proteasome-dependent degradation via its association with the Hrd1-SEL1L ubiquitin ligase complex (5).