LGALS4 (galectin-4) is a carbohydrate-binding protein that plays multifaceted roles in cancer progression and immune regulation. In colorectal cancer, LGALS4 expression is significantly reduced in clinical tissue samples, with TP53 mutations potentially mediating this downregulation 1. When overexpressed, LGALS4 improves the tumor immune microenvironment by activating the CCL4/CCR5 axis through NF-κB signaling, promoting macrophage recruitment and synergizing with anti-PD-L1 therapy 1. LGALS4 demonstrates differential roles across cancer types - its downregulation is associated with acquired oxaliplatin resistance in colorectal cancer 2, while upregulation occurs in certain immune contexts in bladder cancer 3. The protein undergoes unconventional secretion via ATG9A vesicles, independent of classical autophagy pathways 4. Proteome-wide association studies have identified LGALS4 as exhibiting non-linear associations with venous thromboembolism 5 and as a candidate causal protein for cardiovascular diseases through Mendelian randomization approaches 6. Systematic reviews confirm LGALS4's multifaceted role in cancer, with differential expression patterns observed across various cancer stages and types, particularly in digestive system malignancies 7.