Rassf2, belonging to the Ras-association domain family of proteins, is a tumor suppressor gene [1,2,4,5,6]. It contains Ras-association and SARAH domains, and is involved in multiple biological processes. It may be associated with the Hippo signalling pathway, and functions in regulating apoptosis, cell growth and differentiation [2,3].

In gastric cancer, Rassf2 has a significantly higher level of methylation, which can predict the risk of gastric cancer but may not be feasible for predicting tumor metastasis [1]. In Ewing sarcoma, Rassf2 methylation is frequent and correlates with poor overall survival, especially in patients under 18 years old [4]. In squamous cervical cancer, Rassf2 hypermethylation is predominant, related to lower expression, vascular invasion and shorter survival time [5]. Ablation of Rassf2 in mice leads to bone defects and haematopoietic anomalies, as it suppresses osteoblastogenesis but promotes osteoclastogenesis, regulating osteoblast and osteoclast differentiation by inhibiting NF-κB signalling [7].

In conclusion, Rassf2 is a crucial tumor suppressor gene. Its methylation status is closely related to the prognosis of several cancers. The Rassf2 knockout mouse model reveals its important role in bone remodelling and haematopoiesis, providing insights into the understanding of related diseases and potential treatment strategies.