Rassf4, short for Ras-association domain family 4, is a protein-coding gene often regarded as a tumor suppressor regulated by DNA methylation. It participates in multiple biological processes, influencing cell fate in terms of both death and survival. It is involved in pathways such as the regulation of intracellular store-operated Ca2+ entry, and has an impact on the Hippo signaling pathway [1].

In metabolic dysfunction-associated steatotic liver disease (MASLD), liver-specific Rassf4 knockout mice demonstrated that loss of hepatic Rassf4 exacerbated hepatic steatosis and fibrosis. Conversely, Rassf4 overexpression prevented steatosis in MASLD mice. Rassf4 in hepatocytes also suppressed the activation of hepatic stellate cells by reducing transforming growth factor beta secretion. These findings establish Rassf4 as a potential therapeutic target for MASLD and hepatocellular carcinoma (HCC) [2]. In colorectal cancer, Rassf4 was downregulated. Ectopic expression of Rassf4 in LoVo cells inhibited cell growth, colony formation, cell cycle progression, increased 5-FU-induced apoptosis, and downregulated the mitochondrial membrane potential through the YAP/Bcl-2 signaling pathway [3].

In conclusion, Rassf4 plays crucial roles in various biological processes, especially in maintaining cellular homeostasis and in disease contexts such as MASLD, HCC, and colorectal cancer. The use of gene knockout mouse models, like the liver-specific Rassf4 knockout mice, has been instrumental in uncovering its functions in these disease areas, providing insights into potential therapeutic strategies.