CEACAM1 is a cell adhesion molecule that mediates calcium-independent homophilic cell-cell interactions and plays critical roles in immune regulation and disease pathogenesis. Functionally, CEACAM1 promotes regulatory T cell populations controlling IgA production and microbiota homeostasis 1. Mechanistically, CEACAM1 acts as a heterophilic ligand for the immune checkpoint receptor TIM-3, forming both cis and trans interactions through their N-terminal immunoglobulin-variable domains 1. This interaction is essential for TIM-3-mediated T cell inhibition and tolerance induction 1. CEACAM1 also regulates neutrophil activation through S1P signaling, controlling susceptibility to NETosis via its long cytoplasmic isoform (CC1-L) 2. In cancer, CEACAM1 expression on cancer stem cells confers resistance to NK cell-mediated cytotoxicity through homophilic interactions 3. Additionally, CEACAM1 fucosylation by hepatic SLC35C1 attenuates cholestatic liver inflammation by suppressing chemokine expression 4. Clinically, CEACAM1 serves as a biomarker in colorectal, lung, pancreatic, and hepatic malignancies 5. Co-blockade of CEACAM1 and TIM-3 enhances anti-tumor immunity and tumor elimination 1, while blocking CEACAM1 on cancer cells or NK cells improves anti-tumor responses 3.