JAM2 is a junctional adhesion molecule that mediates heterotypic cell-cell interactions with its cognate receptor JAM3 to regulate cellular adhesion and migration 1. Primary function involves hematopoietic stem cell homing and retention in bone marrow through expression on stromal cells 2, and facilitating leukocyte extravasation via tethering and rolling along endothelium, mechanisms dependent on integrin α4β1 binding 34. JAM2 plays roles in spermatogenesis, myogenesis, and potentially angiogenesis through cell-cell adhesion complexes. In cancer biology, JAM2 functions as a tumor suppressor. In lung adenocarcinoma, reduced JAM2 expression correlates with poor prognosis and increased metastasis, while overexpression suppresses proliferation and epithelial-mesenchymal transition 5. Similarly in breast cancer, high JAM2 expression predicts favorable prognosis and inhibits invasion through EMT pathway suppression 6. JAM2 also contributes to immunosuppression when expressed by carcinoma-associated fibroblasts in triple-negative breast cancer, retaining regulatory T lymphocytes 7. Clinically, JAM2 mutations (autosomal recessive) cause Primary Familial Brain Calcification (Fahr's disease), characterized by bilateral basal ganglia calcification with movement, cognitive, and psychiatric manifestations 8910. Pathogenic JAM2 variants disrupt blood-brain barrier integrity and endothelial function, causing calcium-hydroxyapatite deposition. JAM2 is upregulated in hyperglycemic lung disease, potentially indicating therapeutic stem cell effects 11.