The small-molecule inhibitor HA15, a thiazole benzenesulfonamide that specifically inhibits HSPA5 ATPase activity, was shown to activate the UPR-signaling in melanoma by disrupting its interaction with PERK, IRE1, and ATF6 and demonstrated to overcome BRAF therapy resistance of the cancer cells in vitro as well as in xenograft analyses [58]. The gene discussed is ERN1; the disease is cancer.