OPCML is a glycosyl phosphatidylinositol (GPI)-anchored cell adhesion molecule belonging to the IgLON family 1. It functions primarily as a tumor suppressor that is silenced in over 80% of ovarian cancers through loss of heterozygosity and epigenetic mechanisms, particularly promoter hypermethylation 1. OPCML exerts its anti-cancer effects by downregulating receptor tyrosine kinases (RTKs) including EphA2, FGFR1, FGFR3, HER2, HER4, and AXL 1. In colorectal cancer, OPCML restoration reverses epithelial-to-mesenchymal transition by inactivating TGFβ-Smad signaling 2. Beyond oncology, OPCML plays critical roles in synaptic biology through the ephrin-EphB2-cofilin signaling pathway, regulating spine maturation and cognitive behaviors 3. Loss of OPCML produces schizophrenia-like phenotypes including impaired cognition and abnormal sensorimotor gating in mice, which respond partially to antipsychotic treatment 3. In ovarian cancer diagnosis, OPCML methylation in circulating cell-free DNA shows superior performance as a methylation biomarker compared to RASSF1A and BRCA1 4. OPCML's therapeutic potential extends to sensitizing cancers to kinase inhibitors like lapatinib and erlotinib 1.