RASSF5 (NORE1A) is a tumor suppressor protein that functions as a scaffolding molecule connecting Ras signaling to multiple cellular pathways 1. The protein contains a Ras Association domain and lacks intrinsic enzymatic activity, serving primarily as a localization and scaffolding protein 1. RASSF5 is a key upstream component of the Hippo pathway, where it regulates MST1/2 kinases through SARAH domain interactions 2. Mechanistically, RASSF5 can both inhibit and activate MST1/2 depending on the temporal context - it blocks MST2 autoactivation when binding before phosphorylation but does not inhibit already activated MST2 2. The protein undergoes frequent epigenetic silencing through promoter hypermethylation in various cancers including neuroblastoma, where methylation correlates with MYCN amplification and poor prognosis 34. RASSF5 connects Ras to diverse signaling pathways controlling apoptosis, senescence, cell cycle regulation, and differentiation 4. Recent studies reveal RASSF5 also plays a role in metabolic regulation, as its loss promotes fatty liver disease (MASLD/MASH) development through upregulation of SREBP1 and disruption of liver metabolism 5. The frequent inactivation of RASSF5 in tumors disconnects Ras from pro-death signaling, enhancing transformation and metastasis 1.