Neo1, also known as Neogenin-1, is a multifunctional gene. It encodes a transmembrane receptor and belongs to a highly conserved subfamily of P-type ATPase genes in yeast, encoding phospholipid flippases [5,7,8]. As a receptor, it is involved in multiple signaling pathways, such as those related to cell migration, differentiation, and neurulation. In cell migration, its ligands Netrin-1 and repulsive guidance molecule (RGM) can bind simultaneously, forming a complex that regulates extracellular signaling [2]. In neurulation, the Rgma/Neo1 signaling pathway promotes neuroepithelial cell elongation [3].

In disease-related studies, in subarachnoid hemorrhage (SAH) models and NEO1GFAP-Cre (a conditional knockout, CKO) mice, loss of astrocytic NEO1 led to exacerbated endothelial cell (EC) dysfunction and increased blood-brain barrier (BBB) permeability, while hepcidin administration mitigated these effects, highlighting NEO1's importance in BBB integrity post-SAH [1]. In colorectal cancer, NEO1 is down-regulated, and overexpression of NEO1 in CRC cells restrained their proliferation, migration, and invasion, suggesting it as a potential prognostic biomarker [4]. In acute myocardial infarction, macrophage-specific Neo1 deficiency (induced by Neo1flox/flox;Cx3cr1cre mice, a CKO model) exacerbated myocardial remodeling and inflammation through the JAK1-STAT1 signaling pathway [6].

In conclusion, Neo1 plays essential roles in multiple biological processes including cell migration, neurulation, and maintaining the integrity of physiological barriers. Its dysfunction is associated with various diseases such as SAH, colorectal cancer, and myocardial infarction. Studies using KO or CKO mouse models have been crucial in revealing its function in these disease conditions, providing potential targets for therapeutic intervention.