IGSF9 (immunoglobulin superfamily member 9) is an immunoglobulin superfamily adhesion molecule with a conserved structural organization similar to neural cell adhesion molecules, containing five immunoglobulin domains and two fibronectin type III repeats 1. Developmentally, IGSF9 is expressed in the nervous system from embryonic stages and functions in dendrite outgrowth, axon guidance, synapse maturation, and neuronal self-avoidance 2. The protein mediates homophilic cell-cell adhesion through its extracellular and intracellular domains 2. Beyond neural development, IGSF9 has emerged as a multifunctional protein in cancer biology and metabolism. As a tumor-specific immune checkpoint, IGSF9 is induced by interferon-gamma signaling in acute myeloid leukemia and promotes tumor immune escape by inhibiting T cell activity 3. IGSF9 also promotes tumor invasion and metastasis through GSK-3β/β-catenin-mediated epithelial-to-mesenchymal transition in lung cancer 4, while functioning as a p53 target gene that suppresses breast cancer metastasis via FAK/AKT pathway inhibition 5. Additionally, IGSF9 educates tumor-associated macrophages toward senescence and immunosuppressive phenotypes through TMUB1 binding and IL-6/STAT3 activation 6. Clinically, IGSF9 downregulation associates with lymph node metastasis and poor survival in breast cancer 7, and elevated plasma IGSF9 correlates with liver steatosis and fibrosis in HIV-positive individuals 8.