Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation (PubMed:11779465). The active endoribonuclease domain splices xbp-1 precursor mRNA to produce the mature form which then induces transcription of UPR target genes (PubMed:11779465). Unfolded protein response (UPR) transcriptional activation by ire-1, as well as translational attenuation by pek-1 in a complementary pathway, maintains ER homeostasis (PubMed:11779465, PubMed:16184190). Regulates the transcriptional up-regulation of nucleoside-diphosphatase apy-1 and many other genes, upon ER stress (PubMed:18216284, PubMed:16184190). By activating the UPR pathway during non-lethal hypoxia pre-conditioning, confers adaptive protection to subsequent exposure to hypoxia (PubMed:20733002). ire-1 and pek-1 are redundant genes that control a pathway essential for larval development and survival (PubMed:11779465, PubMed:16184190). Plays a role in the nuclear retention of unspliced mRNAs (PubMed:23149939). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain (By similarity). Autophosphorylated mainly on serine residues. In combination with RNAi-mediated knockdown of atf-6, causes sluggish movement, arrested development at the L2 larval stage, and lethality soon thereafter; larvae have intestinal degeneration and develop many vacuoles in the intestinal cells (PubMed:16184190). In combination with RNAi-mediated knockdown of pek-1, larvae have intestinal degeneration and develop many vacuoles in the intestinal cells (PubMed:16184190). RNAi-mediated knockdown restores fertility, reduces the accumulation of unspliced tra-2 in the cytoplasm and suppresses germ line masculinization caused by RNAi-mediated knockdown of rnp-4/RBM8A (PubMed:23149939). Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.