SEC61A1 encodes the alpha-1 subunit of the SEC61 translocon complex, a fundamental component of the endoplasmic reticulum (ER) protein translocation machinery. As the primary channel-forming component, SEC61A1 mediates cotranslational transport of signal peptide-containing nascent polypeptides across the ER membrane and cooperates with auxiliary proteins SEC62, SEC63, and HSPA5/BiP for post-translational translocation 1234. The protein functions as both a ribosome receptor and gated pore, essential for proper protein synthesis targeting 23. SEC61A1 also facilitates ER membrane insertion of transmembrane proteins and maintains calcium homeostasis through passive efflux regulation 35. Pathologically, mutations in SEC61A1 cause autosomal dominant tubulointerstitial kidney disease (ADTKD-SEC61A1), characterized by progressive tubular damage, interstitial fibrosis, and early-onset chr3 kidney disease, often accompanied by extrarenal manifestations including hematological abnormalities, growth retardation, and hyperuricemia 67. A SEC61A1 variant has also been associated with polycystic liver disease through impaired polycystin-2 biosynthesis 8. Beyond genetic kidney disease, dysregulated SEC61A1 expression has been implicated in multiple myeloma and nasopharyngeal carcinoma progression through regulatory RNA pathways 910.