Ras association domain-containing protein 5 (RASSF5)

Ras association domain-containing protein 5 (RASSF5) is a cytosolic tumor suppressor and adaptor protein that acts primarily as a Ras-binding effector, integrating signals from GTP-bound Ras family GTPases through its extended Ras-association (RA) domain[1][3][4][5]. RASSF5 contains a C-terminal SARAH (Sav/RASSF/Hippo) domain that mediates interaction with Hippo pathway kinases MST1/2, linking oncogenic Ras signaling and the Hippo tumor-suppressing pathway[2][3][4]. In normal physiological conditions, RASSF5 regulates Ras-dependent apoptosis, cell cycle arrest, and senescence, and also controls lymphocyte adhesion, cell polarization, cytoskeletal dynamics, and migration[1][3][4][6]. Loss or inactivation of RASSF5, typically through promoter hypermethylation or deleterious mutations, is associated with cancer development and progression in multiple tissues[1][3][5][6]. While RASSF5 itself is not currently a direct clinical drug target, its silencing or dysfunction is a frequent event in human tumors, and restoring its tumor-suppressive functions is a promising therapeutic strategy in Ras-driven malignancies[1][3][5].

Other names

NORE1NORE1ANORE1BRAPLMaxp1New ras effector 1Regulator for cell adhesion and polarization enriched in lymphoid tissuesRap1-binding proteinTumor suppressor RASSF5

RASSF5 functions primarily as a scaffold and tumor suppressor; any targeted therapy would likely aim to enhance RASSF5 activity, block its inactivation (e.g., demethylating agents if silenced by methylation), or prevent oncogenic Ras from bypassing its suppressive function