Sec61a1 encodes a subunit of the translocation machinery of protein biosynthesis at the endoplasmic reticulum (ER), which is crucial for the proper insertion and translocation of newly synthesized proteins into the ER lumen or membrane [2]. This process is fundamental for the normal function of cells and is involved in multiple biological pathways related to protein processing and trafficking.

Mutations in SEC61A1 are associated with several diseases. In autosomal dominant tubulointerstitial kidney disease (ADTKD), SEC61A1 is one of the genes whose mutations can lead to the disease, which is characterized by tubular damage and interstitial fibrosis progressing to end-stage renal disease [1,3,7]. A SEC61A1 variant has also been associated with autosomal dominant polycystic liver disease, where the mutant SEC61A1 shows increased proteasomal degradation and impairs the biosynthesis of polycystin-2 (PC2) [2,6]. In addition, high SEC61A1 expression is related to poor outcomes in acute myeloid leukemia, and it may be an independent risk factor for predicting survival in patients undergoing allo-HSCT [5]. Circ_SEC61A1, a circular RNA, contributes to the progression of multiple myeloma cells by regulating the miR-660-5p/CDK6 axis [4].

In conclusion, Sec61a1 is essential for protein biosynthesis at the ER. Studies related to SEC61A1 mutations have revealed its significance in various disease conditions, especially in kidney and liver cystic diseases, as well as in certain cancers. Understanding the role of Sec61a1 through these disease-related associations provides insights into the underlying molecular mechanisms of these diseases and may potentially lead to new therapeutic strategies.