GLIPR2 (GLI pathogenesis related 2) is a Golgi-associated protein with context-dependent roles in cellular pathophysiology. As a negative regulator of autophagy, GLIPR2 inhibits the BECN1-ATG14-containing phosphatidylinositol 3-kinase complex (PtdIns3K-C1), directly binding to and suppressing its lipid kinase activity 1. GLIPR2 depletion increases autophagic flux and promotes Golgi reorganization 1. In cardiovascular disease, GLIPR2 promotes endothelium-mesenchymal transition (EndoMT) and cardiac fibrosis following acute myocardial infarction through the PDGFRL/AKT/mTOR signaling pathway 2. GLIPR2 knockdown reverses EndoMT, attenuates fibrosis, and partially restores ventricular function 2. Conversely, GLIPR2 functions as a tumor suppressor in lung adenocarcinoma, with reduced expression in neoplastic tissues correlating with poor prognosis and decreased immune infiltration 3. Elevated GLIPR2 associates with improved outcomes and enhanced radiation sensitivity 3. In diabetic nephropathy, GLIPR2 expression correlates with pathogenic progression via the NEAT1/miR-423-5p and circACTR2/miR-140-5p axes 4, 5. In non-alcoholic fatty liver disease, elevated GLIPR2 contributes to inflammation and steatosis through NLRP3 signaling, with therapeutic agents reducing GLIPR2 to promote protective autophagy 6. These divergent roles underscore tissue- and context-specific regulation of GLIPR2 function.