TRAM1 (translocation-associated membrane protein 1) is a multifunctional endoplasmic reticulum (ER) membrane protein with roles in both viral pathogenesis and cellular protein biogenesis. Primary function: TRAM1 facilitates ER protein import and membrane insertion, serving as an auxiliary component of the Sec61 translocon complex 1. Its mechanism likely involves modulating the phospholipid bilayer near the Sec61 lateral gate to support nascent polypeptide translocation 2. Disease relevance: TRAM1 participates in human cytomegalovirus (hCMV) immune evasion by forming complexes with viral proteins US2 and US11 to promote ER-to-cytosol dislocation and proteasomal degradation of MHC class I heavy chains, reducing immune detection 3. Additionally, TRAM1 interacts with SARS-CoV-2 NSP3 protein at viral replication organelles, promoting coronavirus replication 4. Clinical significance: The TRAM1 gene (located at chromosome 8, though also annotated at 20q12 as SRC-3/AIB1) shows amplification and overexpression in multiple human cancers, including esophageal squamous cell carcinoma and breast cancer, correlating with increased cell proliferation and tumor progression 56. Emerging therapeutic applications include delivering TRAM1 protein via engineered extracellular vesicles for intervertebral disc degeneration repair 7.