IgSF9, also known as immunoglobulin superfamily member 9 or Dasm1, is a member of an evolutionarily ancient protein family. Like the neural cell adhesion molecule family, IgSF9 family members are expressed in the nervous system and have been implicated in neurite outgrowth, axon guidance, synapse maturation, self-avoidance, and tiling [1]. In addition, they may be involved in cell adhesion processes.

In Drosophila, the IgSF9-related protein Borderless (Bdl) is required for axonal transport of synaptic-vesicle components in photoreceptor R8 axons, and its loss causes a failure of R8-dependent phototaxis response to green light [6]. In cancer research, in lung cancer, IgSF9 promotes tumor invasion and metastasis through GSK-3β/β-catenin mediated epithelial-to-mesenchymal transition (EMT) [2]. In breast cancer, IgSF9 is trans-activated by p53 and inhibits breast cancer metastasis by modulating FAK/AKT signaling pathway. Low expression of IgSF9 is associated with lymph node metastasis and poor prognosis in breast cancer patients [3,4,5]. In endometrial cancer, IgSF9 is overexpressed, and its expression is associated with myometrium invasion and poor prognosis [8]. Also, IgSF9 is amongst the top differentially expressed proteins associated with both liver steatosis and fibrosis in people living with HIV [7].

In conclusion, IgSF9 plays crucial roles in both nervous system development and function, as well as in various cancer-related processes such as metastasis and in liver steatosis and fibrosis. The study of IgSF9 in different genetic models helps to understand its diverse functions and provides potential targets for treating related diseases.