Ras association domain family member 5 (RASSF5, also named NORE1) is an identified member of the RASSF gene family which could bind selectively to activate Ras and function as an antineoplastic effector in multiple cellular regulations. While highly expressed in majority of normal tissues, RASSF5 is epigenetically inactivated by promoter hypermethylation in numerous cancer cell lines and primary cancers, suggesting it as a potential tumor suppressor. Nevertheless, the physiologic significance of RASSF5 in tumorigenesis remains unclear. We performed a systematic literature review and assessment from PUBMED and MEDLINE databases in this article. RASSF5 is involved in a series of cellular responses including apoptosis, senescence, cell cycle regulation, differentiation and cell proliferation and the inactivation of RASSF5 has been implicated to participate in the oncogenesis, progression and poor prognosis of human cancers. In this review, we mainly elucidate the acknowledged structure, progress in the verified functions and research advances of RASSF5 and the probably relevant signaling pathways. Based on these evidences, potentiality of RASSF5 as a new therapeutic target for human cancers may play a significant role in future oncotherapy.
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