Activated IRE1α/XBP1s pathway in myofibroblasts contributes ER biogenesis, which helps in adaptation to increased protein folding requirement in myofibroblastsIRE1α/XBP1s pathway may also contribute in efficient protein folding by providing ER chaperones, such as glucose-regulated protein 78IRE1α/RIDD pathway degrades miRNA-150, a repressor αSMA and collagen I and IV expression, which results in enhanced fibrosisIRE1α/JNK/AP1 and IRE1α/NFκB pathways possibly involved endothelin-1 expression in systemic sclerosis. Here, NFKB1 is linked to systemic sclerosis.