Acetyl‐lysine‐mimicking molecular compounds such as JQ1 and I‐BET can inhibit oncogenic transcriptional programs through synergistically competing with BRD4 in acetyl‐lysine chromatin‐binding modules.42 Herein, we reported that GLTSCR1‐KO and CRISPR‐mediated heterozygous mutated CRC cells exhibited decreased sensitivity to JQ1 and I‐BET, indicating that mutations in GLTSCR1 might be considered as biomarkers for traditional BET inhibitor resistance in CRC. The gene discussed is BICRA; the disease is colorectal carcinoma.