ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270).

Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059)

Homodimer; disulfide-linked. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (By similarity). Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX.

Interacts with AIMP1; regulates its retention in the endoplasmic reticulum. Hyperglycosylated form interacts with OS9; promoting its degradation by the endoplasmic reticulum associated degradation (ERAD) (PubMed:18264092, PubMed:24899641). Interacts with CNPY3.

This interaction is disrupted in the presence of ATP (By similarity). Interacts with TLR4 and TLR9, but not with TLR3 (PubMed:20865800). Interacts with MZB1 in a calcium-dependent manner (By similarity).

Interacts with METTL23 (PubMed:23349634). Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC (PubMed:32272059). Interacts with EIF2AK3 (PubMed:11907036)

The SRT pseudosubstrate motif associates with STT3A during translation in normal conditions, preventing glycosylation of facultative sites until HSP90B1 folding is completed