STT3B is the catalytic subunit of the OST-B oligosaccharyltransferase complex, catalyzing transfer of a high-mannose glycan (Glc3Man9GlcNAc2) from dolichol-pyrophosphate to asparagine residues in the Asn-X-Ser/Thr consensus motif of nascent polypeptides 1. Unlike STT3A which primarily mediates cotranslational N-glycosylation, STT3B specializes in post-translational glycosylation and can modify nascent sites inaccessible to STT3A 2. STT3B contains the active site and binding pockets for acceptor peptides and donor oligosaccharides 1. The complex associates with the Sec61 translocon during protein translocation across the endoplasmic reticulum 3. STT3B participates in ER-associated degradation by glycosylating misfolded proteins, marking them for ubiquitin-dependent degradation 2. Disease relevance includes congenital disorder of glycosylation 1X. Emerging evidence demonstrates STT3B's critical role in pathological processes: STT3B-mediated N-glycosylation of EREG stabilizes this growth factor, promoting PDL1 upregulation and immune evasion in head and neck squamous cell carcinoma 4; STT3B regulates CTSD glycosylation affecting colorectal cancer liver metastasis through ferroptosis pathways 5; and STT3B-dependent TPC2 glycosylation blocks autophagy, aggravating pulmonary arterial hypertension 6. STT3B is essential for coronavirus spike protein glycosylation required for viral replication 7, while STT3B inhibition by indocyanine green protects against α-amanitin toxicity 8.