CXCL6 (C-X-C motif chemokine ligand 6), also known as granulocyte chemoattractant protein-2 (GCP-2), is a chemokine that functions primarily as a neutrophil chemoattractant 1. It signals through binding to CXCR1 and CXCR2 receptors 2 and recruits neutrophils to inflammatory sites 1. Beyond its chemotactic role, CXCL6 possesses strong antibacterial activity and angiogenic properties 1. Mechanistically, CXCL6 activates multiple intracellular pathways including JAK-STAT, ERK1/2, and PI3K signaling cascades 23. In cancer contexts, CXCL6 induces tumor cell stemness and promotes neutrophil extracellular trap (NET) formation, which leads to immunotherapy resistance by blocking CD8+ T cell infiltration 2. CXCL6-CXCR2 interactions also recruit neutrophils and modulate immune cell polarization in the tumor microenvironment 4. CXCL6 is dysregulated in multiple diseases. In hepatocellular carcinoma, CXCL6 overexpression activates the JAK-STAT3 pathway in hepatocytes, promoting local immunosuppression and tumor progression 5. Elevated CXCL6 is associated with cholangiocarcinoma progression and lipid metabolic reprogramming 2. Additionally, systemic CXCL6 levels are elevated in lumbar disc degeneration and may serve as a biomarker for disease severity 6. Clinically, CXCL6 represents a potential therapeutic target for cancer and inflammatory diseases 1, with pathway inhibition showing promise in preclinical models.