SSR3 (signal sequence receptor subunit 3) is a key component of the translocon-associated protein (TRAP) complex that facilitates protein translocation across the endoplasmic reticulum (ER) membrane 1. Unlike other TRAP subunits that are primarily luminal, SSR3's extramembranous portion is primarily cytosolic 2. The protein plays a crucial role in cotranslational and posttranslational translocation of proteins into the ER, with particular importance in preproinsulin translocation for insulin biosynthesis 2. SSR3 functions as a rate-limiting factor in glucose-dependent proinsulin synthesis, with glucose exposure rapidly upregulating both SSR3 and proinsulin protein levels 2. Pathogenic variants in SSR3 cause congenital disorders of glycosylation (CDG) by destabilizing the TRAP complex and disrupting protein glycosylation 1. In cancer contexts, SSR3 acts as an oncogene with elevated expression correlating with poor prognosis in hepatocellular carcinoma 3 and predicting paclitaxel susceptibility in breast cancer and glioblastoma through regulation of ER stress sensor IRE1α phosphorylation 4. SSR3 also serves as a potential biomarker for immunotherapy response, with high expression indicating an immunosuppressive tumor microenvironment 5.