RACK1 is a multifunctional scaffolding protein that regulates diverse cellular processes through protein-protein interactions and post-translational modifications. Mechanistically, RACK1 serves as a critical adaptor protein that binds transcription factors (such as Pax5) 1 and signaling kinases (including ZAK at collided ribosomes) 2 to modulate their stability and activation. RACK1 also participates in translational control by interacting with eIF4E and PKCβII to regulate oncogene translation 3, 4. RACK1 expression is tightly regulated by ubiquitination and SUMOylation: SMURF2 targets RACK1 for proteasomal degradation through K48-linked ubiquitination 5, while SENP3 deSUMOylation and OTUB1 non-canonical ubiquitination stabilize RACK1 3, 4. In the immune microenvironment, elevated RACK1 promotes M2 macrophage polarization via NF-κB signaling in oral cancer 6. Clinically, RACK1 dysregulation associates with multiple malignancies including ovarian, oral squamous cell, and hepatocellular carcinomas, where elevated expression correlates with poor prognosis 5, 6, 3. Additionally, RACK1 is essential for normal B-cell development 1 and prenatal cortical development, where FMRP-mediated regulation maintains normal mitochondrial function and neuronal excitability 7.