RRAD, also known as Ras-related associated with diabetes, is a member of the Ras-related GTPase superfamily. Primarily a cytosolic protein that acts in the plasma membrane, it is highly expressed in type 2 diabetes patients and serves as a biomarker for congestive heart failure. RRAD is involved in multiple cellular activities including cell division, motility, apoptosis, and energy metabolism, and is regulated through various pathways [1].

RRAD shows dual roles in cancer. In gastric and colorectal cancer, its inhibition significantly declined tumor cell proliferation in vitro and in vivo, reduced cell invasion, decreased EMT markers, angiogenesis, and associated proteins levels, suggesting it as a potential therapeutic target [2]. In hepatocellular carcinoma, RRAD suppresses the Warburg effect by downregulating ACTG1, retarding tumor growth, and is associated with better prognosis [3]. In contrast, in glioblastoma multiforme, RRAD promotes EGFR-mediated STAT3 activation, enhancing self-renewing ability, tumorigenesis, and inducing temozolomide resistance [4]. In pancreatic cancer, SETD8 inhibits ferroptosis by suppressing RRAD expression, and in oral squamous cell carcinoma, downregulation of RRAD in the tumor margin promotes energy metabolism and tumor progression [5,6]. Also, RRAD is up-regulated in cellular senescence and acts as a negative regulator to counter it by reducing reactive oxygen species levels [7].

In conclusion, RRAD is a multifunctional gene involved in diverse biological processes, especially in energy metabolism and cell growth regulation. Its dual role in cancer, as both an oncogene and a tumor suppressor depending on the cancer type, makes it a potential target for cancer therapies. Additionally, its role in senescence further highlights its importance in understanding aging-associated diseases.