The TRAP complex (SSR1–SSR4): mechanistic roles and therapeutic opportunities

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with a poor prognosis, and its molecular mechanisms remain unclear. Our previous research identified the signal sequence receptor subunit delta (SSR4) of the TRAP complex as a potential ESCC biomarker. The TRAP complex, composed of SSR1, SSR2, SSR3, and SSR4, is essential for protein translocation, folding, and quality control, crucial for cellular balance. While individual TRAP subunits have been studied, a comprehensive understanding of their roles in human diseases is lacking. This review synthesizes current evidence on the TRAP complex and its subunits (SSR1-SSR4) to clarify their roles in tumor progression and other diseases, identify knowledge gaps, and evaluate their potential as therapeutic targets. The study shows that TRAP subunit genes are significantly upregulated in various cancers, influencing tumor progression and immune infiltration, with some subunits showing different responses to chemotherapy. A pan-cancer analysis highlights their roles, while SSR3 and SSR4 mutations are linked to congenital glycosylation disorders. SSR1 and SSR3 are essential for glucose metabolism and are associated with diabetes risk. The interaction between TRAP and endoplasmic reticulum stress suggests potential therapeutic applications. This review emphasizes the crucial roles of the TRAP complex and its subunits (SSR1-SSR4) in various diseases, highlighting their potential as therapeutic targets and biomarkers. Future research should focus on understanding the mechanisms through integrated experimental and multi-omics approaches, defining subunit interactions, and exploring structure-based drug design for clinical applications.