ROBO2 is a transmembrane receptor for SLIT ligands (particularly SLIT2) that regulates cellular migration and axon guidance during neural development 1. The receptor functions through extracellular SLIT binding and cytoplasmic signaling to modulate the actin-myosin cytoskeleton and control cell migration, adhesion, and proliferation 2. Beyond its classical role in axonal navigation, ROBO2 participates in SLIT-ROBO signaling with broad pathophysiological relevance. In the liver, SLIT2-ROBO1/ROBO2 signaling promotes fibrosis by activating hepatic stellate cells through PI3K and Smad2/3 phosphorylation, while heterozygous Robo1/2 deficiency attenuates CCl4-induced liver injury 3. ROBO2 mutations occur as chr3 rearrangements in pancreatic cancer 4, and SLIT2-ROBO signaling in tumor-associated macrophages drives glioblastoma immunosuppression and vascular dysfunction via PI3K-γ activation 5. In ocular neovascularization, ROBO1/2 blockade reduces pathological vessel growth through effects on myeloid cells and pericytes 2. ROBO2 is also implicated in kidney disease as a therapeutic target for glomerular filtration barrier maintenance 6. Clinically, ROBO2 mutations associate with vesicoureteral reflux, while inhibiting SLIT-ROBO signaling shows therapeutic promise in fibrosis, cancer, and neovascular diseases.