Importantly, we identify ROCK1 as a mediator of SREBP1 activation, extending the current understanding of SREBP1 regulatory mechanisms.[47] Clinically, targeting ARL5B may achieve dual benefits: 1) ARL5B levels could guide personalized treatment and prognosis assessment in ESCC, and 2) combining existing ROCK1 inhibitors (e.g., fasudil) with SREBP1 inhibitors (e.g., fatostatin) may enhance therapeutic efficacy in ARL5B‐high tumors. This evidence concerns the gene SREBF1 and esophageal squamous cell carcinoma.