CKAP4 (cytoskeleton-associated protein 4) is a multifunctional cell surface receptor with emerging roles in cancer progression and immune regulation. Originally characterized as a high-affinity receptor for the antiproliferative factor APF, CKAP4 has been identified as a critical node in multiple disease-promoting pathways 1. In the tumor microenvironment, AEBP1 binds CKAP4 on cancer-associated fibroblasts to activate AKT/PD-L1 signaling, driving T cell dysfunction and tumor immune evasion 1. Similarly, DKK1 engages CKAP4 on macrophages to activate PI3K-AKT signaling, promoting immunosuppression in gastric cancer 2. CKAP4 also serves as a receptor for bacterial pathogen-associated molecules; the oral pathogen Parvimonas micra surface protein TmpC binds CKAP4 to facilitate OSCC metastasis through HIF-1α and autophagy activation 3. In hepatocellular carcinoma, CKAP4 stabilizes the reticulophagy receptor RETREG1 by competing with TRIM21-mediated ubiquitination, promoting cancer progression 4. Beyond cancer, CKAP4 is upregulated in activated cardiac fibroblasts following ischemic injury, suggesting roles in fibrosis 5. These findings position CKAP4 as a therapeutic target, with CKAP4 antagonism showing promise in enhancing immunotherapy efficacy and suppressing pathogen-driven metastasis.