SEC61B encodes a core component of the SEC61 translocon complex, which mediates cotranslational translocation of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER) membrane 1. The protein functions as both a ribosome receptor and gated pore in the ER membrane, essential for nascent polypeptide translocation 1. SEC61B cooperates with TRAM1 to import newly synthesized proteins into the ER and mediates membrane insertion of initial transmembrane segments of multi-pass proteins, with subsequent segments inserted by the multi-pass translocon complex 1234. SEC61B mutations cause autosomal dominant polycystic liver disease (ADPLD) and contribute to autosomal dominant polycystic kidney disease (ADPKD) 56. Loss-of-function SEC61B variants trigger cyst formation through defective maturation and trafficking of polycystin-1, the central disease determinant 67. In a large clinical cohort, SEC61B variants were identified among genes causing cystic kidney disease, though less frequently than PKD1/PKD2 mutations 8. SEC61B is also implicated in ER homeostasis maintenance, as its abundance varies in cellular subdomains relevant to reticulophagy and selective ER degradation 910.