Stt3b is one of the catalytically active subunits of the oligosaccharyltransferase (OST) complex. It is mainly involved in the N-glycosylation pathway, which is crucial for the proper folding, stability, and function of many proteins. N-glycosylation can occur cotranslationally and post-translationally, and Stt3b is preferentially associated with post-translational N-glycosylation [5,7,8]. This process is essential for various biological functions, such as cell-surface receptor signaling, tissue development, and the replication of certain viruses [4,3].

Genetic ablation of Stt3b has shown its significance in multiple disease-related and biological processes. In the context of α-amanitin toxicity, a genome-wide CRISPR screen identified Stt3b as required for the toxicity, and its inhibitor indocyanine green (ICG) can serve as an antidote [1]. In head and neck squamous cell carcinoma (HNSCC), knockdown of Stt3b suppressed the glycosylation of Epiregulin (EREG), which is important for PDL1 upregulation and immune evasion, and the inhibitor NGI-1 enhanced the efficacy of immunotherapy [2]. For porcine epidemic diarrhea virus (PEDV), genetic ablation revealed that the Stt3b-OST complex, but not Stt3A, is preferentially required for viral replication by regulating the N-glycosylation of the PEDV S protein [3]. In the case of Lassa virus, knockout of Stt3b, but not Stt3A, caused hypoglycosylation of the viral glycoprotein, affecting virus propagation [6].

In summary, Stt3b plays a vital role in the N-glycosylation of proteins, which is essential for numerous biological processes and is involved in various disease conditions, including toxin-induced toxicity, cancer, and viral infections. Gene knockout models of Stt3b have been instrumental in uncovering its role in these specific biological and disease-related processes, providing potential therapeutic targets for treating associated diseases.