In terms of heart failure, it was shown that XBP1s stimulates adaptive cardiac growth through activation of mTORC1, which is mediated via FKBP11 (FK506-binding protein 11), a novel transcriptional target of XBP1s, thus describing a non-canonical protective for IRE1/XBP1s in pathological hypertrophy (Figure 2A, IRE1/XBPs cardiac hypertrophy) (36). The gene discussed is ERN1; the disease is heart failure.