SSR4 (signal sequence receptor subunit 4) is a subunit of the translocon-associated protein (TRAP) complex, which is essential for protein translocation across the endoplasmic reticulum (ER) membrane and co-translational translocation through the Sec61 translocon 1. The TRAP complex facilitates efficient N-linked glycosylation of proteins in the ER by participating in protein translocation and folding 2. SSR4 is part of a calcium-binding complex that regulates retention of ER-resident proteins [UniProt]. Mechanistically, SSR4 contributes to protein quality control and may modulate immune cell interactions through the MIF/CD74/CXCR4 axis in tumor microenvironments 3. Pathogenic SSR4 variants cause SSR4-CDG, an ultra-rare X-linked congenital disorder of glycosylation presenting with developmental delay, speech delay, intellectual disability, muscular hypotonia, microcephaly, and distinctive facial features 2. A hallmark biochemical finding is a type 1 serum sialotransferrin profile 4. SSR4 deficiency impairs N-linked glycosylation, with some patients presenting connective tissue abnormalities including redundant skin, joint laxity, and vascular tortuosity 4. Clinically, SSR4 shows elevated expression in multiple cancers, including esophageal squamous cell carcinoma and colon adenocarcinoma, where high expression correlates with immune infiltration, advanced TNM staging, and in colon cancer, improved overall survival 35. In Alzheimer's disease, SSR4 protein expression is upregulated in brain capillaries alongside increased ribosomal and glycosylation machinery 6.