CKLF (chemokine-like factor) is a chemokine with immunomodulatory functions characterized by chemotactic activity toward monocytes, neutrophils, and lymphocytes through CCR4 binding 12. As the founding member of the CKLF-like MARVEL transmembrane domain-containing (CMTM) family, CKLF shares structural features with both chemokines and the transmembrane-4 superfamily, positioning it at the intersection of immune signaling and transmembrane regulation 34. Beyond its chemotactic role, CKLF participates in hematopoiesis and immune system development 3. Clinically, CKLF expression is dysregulated across multiple malignancies. In hepatocellular carcinoma, CKLF is significantly upregulated and serves as an independent prognostic biomarker for overall survival, with expression correlating with immune cell infiltration and checkpoint gene expression 5. In breast cancer and other solid tumors, CMTM family members including CKLF regulate immune checkpoints and tumor progression 6. The CMTM family's involvement in cancer pathogenesis, metastasis, and immune evasion suggests CKLF and related proteins represent novel therapeutic targets for improving immunotherapy and chemotherapy outcomes 78. Further research is needed to fully elucidate CKLF's specific molecular mechanisms in disease contexts.