PAQR3 is a Golgi-scaffold protein that functions primarily as a tumor suppressor by spatially organizing signaling complexes at the Golgi apparatus 1. It serves as a spatial regulator of RAF1 kinase by sequestering it to the Golgi, thereby negatively regulating the Ras/Raf/MEK/ERK pathway 2. Additionally, PAQR3 acts as a positive regulator of cholesterol biosynthesis by anchoring the SCAP:SREBP complex at the Golgi apparatus to promote lipid synthesis. PAQR3 expression is significantly downregulated across multiple human cancers including breast cancer, prostate cancer, glioma, hepatocellular carcinoma, and non-small cell lung cancer 3. Reduced PAQR3 expression correlates with poor patient prognosis and shortened overall and disease-free survival 3. In breast cancer, PAQR3 downregulation inversely correlates with HER2 expression and occurs through promoter hypermethylation in 71.8% of cases 45. PAQR3 overexpression inhibits cancer cell proliferation, migration, and invasion while suppressing epithelial-mesenchymal transition markers 67. The tumor suppressive mechanisms involve inhibition of PI3K/Akt and ERK phosphorylation 7. PAQR3 downregulation is mediated by oncogenic microRNAs including miR-543 and miR-15b-5p 3. These findings position PAQR3 as a potential therapeutic target and prognostic biomarker in cancer management.