SSR1

Signal Sequence Receptor 1 (SSR1), a key endoplasmic reticulum (ER) membrane protein, is widely recognized by its alias TRAPα (Translocon-Associated Protein Alpha) as part of the TRAP complex. Its core function lies in mediating cotranslational translocation: it binds to the Sec61 translocon, stabilizes its structure, and facilitates the recognition of signal sequences on nascent polypeptides, ensuring their proper entry into the ER lumen for folding and modification.
SSR1 activity intersects with pathways governing ER homeostasis, particularly the unfolded protein response (UPR). Dysregulated SSR1 is linked to neurodegenerative disorders (e.g., Alzheimer’s disease, where it disrupts amyloid precursor protein processing) and some cancers. Drug development targeting SSR1 is in early preclinical phases, focusing on small molecules that fine-tune its interaction with the Sec61 complex to restore impaired ER protein trafficking in pathological conditions.