Chronic ER stress and resulting UPR-induced apoptosis is associated with a multitude of human diseases such as neurodegeneration, diabetes and cancer.35–39 Loss of UPR signaling components is associated with a variety of human skeletal dysplasias, therefore suggesting a functional role for UPR signaling in bone cell homeostasis, and insinuating a role for ER stress in bone disease.4,40–43 Of note, mutations in UPR proteins EIF2AK3, ATF4, and ATF6-like cAMP responsive element binding (CREB) transcription factors, have been shown to affect chondrocyte growth and overall bone health. Here, EIF2AK3 is linked to cancer.