ESCC remains a highly aggressive gastrointestinal cancer with persistently poor outcomes despite advances in basic research and clinical research, highlighting underscoring the need for precise therapeutic targets.[29] Here, we identify the first evidence that ARL5B serves as a key driver of ESCC progression via the ARL5B/ROCK1/SREBP1 signaling axis. The gene discussed is SREBF1; the disease is esophageal squamous cell carcinoma.