RPL6 (ribosomal protein L6) is a structural component of the cytosolic 60S ribosomal subunit involved in translation 1. Beyond its canonical ribosomal function, RPL6 serves critical regulatory roles in cellular processes. RPL6 directly binds to HMGCS1 mRNA 3'UTR to stabilize cholesterol biosynthesis enzymes, which indirectly stabilizes HIF-1α and activates hypoxia signaling 2. RPL6 also interacts with CacyBP/SIP to modulate ribosome function and protein synthesis efficiency 3. In disease contexts, RPL6 expression is dysregulated bidirectionally. In gastric cancer and hepatocellular carcinoma (HCC) metastasis, RPL6 is upregulated and promotes cell proliferation, invasion, and poor prognosis through cyclin E-mediated cell cycle progression and cholesterol-HIF-1α signaling 12. Conversely, RPL6 is significantly decreased in primary HCC tissues, where it suppresses tumor growth by stabilizing p53 through competitive binding to E3 ligase FBXO22 4. In glioblastoma, UBE2T-mediated RPL6 degradation promotes malignancy 5. RPL6 is also upregulated in Alzheimer's disease brain capillaries 6 and identified as a biomarker in multi-omics AD studies 7. These findings position RPL6 as a context-dependent oncogenic or tumor-suppressive factor with therapeutic potential.