a result, GRP78 is released from IRE1 to support protein folding. IRE1 oligomerises and activates its ribonuclease domain through auto (self) phosphorylation. Activated IRE1 catalyses the excision of a 26 nucleotide unconventional intron from ubiquitously expressed XBP1u mRNA, in a manner mechanistically similar to pre-tRNA splicing. Removal of this intron causes a frame shift in the XBP1 coding sequence resulting in the translation of a 376 amino acid, 40 kDa, XBP-1s isoform rather than the 261 amino acid, 33 kDa, XBP1u isoform. Moreover, the XBP1u/XBP1s ratio (XBP1-unspliced/XBP1-spliced ratio) correlates with the expression level of expressed proteins in order to adapt the folding capacity of the ER to the respective requirements. Clinical significance Abnormalities in XBP1 lead to a heightened ER stress and subsequently causes a heightened susceptibility for inflammatory processes that may contribute to Alzheimer's disease. In the colon, XBP1 anomalies have been linked to Crohn's disease. A single nucleotide polymorphism, C116G, in the promoter region of XBP1 has been examined for possible associations with personality traits. None were found. Interactions XBP1 has been shown to interact with estrogen receptor alpha. See also Unfolded protein response References