SLIT2 is a secreted axon-guidance ligand that functions as a molecular repellent controlling cellular migration through interaction with roundabout (ROBO) receptors 1. During neural development, SLIT2 acts as a repulsive signal preventing inappropriate midline crossing by axons in the forebrain and spinal cord, and directs retinal ganglion axons along appropriate paths in the developing visual system. In the spinal cord, SLIT2 modulates commissural axon responses to netrin by silencing its attractive effects through ROBO1-DCC complex formation 2. The protein exhibits differential N- and C-terminal activities: the N-product repels olfactory bulb axons while inducing branching in dorsal root ganglia axons. Beyond neural development, SLIT2 regulates immune cell migration and pathological fibrosis. In liver fibrosis, elevated SLIT2-ROBO1 signaling promotes hepatic stellate cell activation through Smad2/3 and PI3K-AKT phosphorylation, independent of TGF-β1 1. In cancer contexts, SLIT2 functions distinctly based on cellular source: tumor-derived SLIT2 activates nociceptive neurons to suppress tumor immunity 3, while endothelial SLIT2 promotes cancer cell intravasation 4. In glioblastoma, tumor-derived SLIT2 recruits macrophages via ROBO1/2-PI3K-γ signaling, driving immunosuppression 5. SLIT2 also regulates fibroblast phenotypes in inflammatory contexts 6. These findings establish SLIT2 as a multifunctional guidance molecule with context-dependent roles in development, immunity, and disease pathogenesis.