The Opioid Binding Protein/Cell Adhesion Molecule-Like (OPCML) gene, located on chromosome 11q25. encodes a glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecule belonging to the IgLON family. Initially identified for its role in neuronal development and synaptic plasticity, OPCML has gained attention as a tumor suppressor gene epigenetically silenced in various cancers, including ovarian, breast, liver, and lung cancers. Its inactivation—often through promoter hypermethylation—correlates with disrupted cell adhesion, signaling, and uncontrolled proliferation. OPCML antibodies are critical tools for studying its expression patterns, epigenetic regulation, and functional interactions in cancer biology. These antibodies enable detection of OPCML protein loss in tumor tissues, aiding in biomarker research and mechanistic studies. OPCML has been shown to inhibit oncogenic receptor tyrosine kinases (e.g., EGFR, HER2) by modulating their endocytosis and downstream pathways. Therapeutic strategies targeting OPCML restoration, such as demethylating agents, are under exploration. Antibodies against OPCML also support prognostic assessments, as its downregulation often predicts poor clinical outcomes. Current research focuses on elucidating its tumor-suppressive mechanisms, including metastasis inhibition via integrin signaling modulation, and its potential synergy with immunotherapy.