Endoplasmic reticulum to nucleus signaling 2 (ERN2)

Endoplasmic reticulum to nucleus signaling 2 (ERN2, also known as IRE1b) is a type I transmembrane serine/threonine-protein kinase and endoribonuclease localized on the endoplasmic reticulum membrane[1][3][5]. It is structurally related to IRE1α (ERN1), but differs in tissue expression and physiological roles. ERN2 is activated by ER stress and contributes to the unfolded protein response (UPR) primarily by inducing translational repression via 28S ribosomal RNA cleavage and potentially promoting apoptosis[1]. Unlike IRE1α, ERN2 does not appear to play a major role in the canonical UPR-associated gene expression but may act as a specialized sensor and effector in certain tissues (e.g., gastrointestinal tract)[1][6]. Alterations in ERN2 function are associated with inflammatory diseases such as ileocolitis and have been implicated in broader proteostasis-related pathologies[1][6].

Other names

IRE1bInositol-requiring protein 2Serine/threonine-protein kinase/endoribonuclease IRE2HIRE2pEndoplasmic reticulum to nucleus signalling 2 (alternate spelling)ER to nucleus signalling 2 (alternate spelling)

For drugs modulating the UPR or ER stress: - Inhibition or enhancement of ERN2 kinase and/or RNase activity - Reduction of ER stress through chaperone activity - Chemical inhibition of rRNA cleavage or translational repression - Modulation of unfolded protein response pathways