Robo2 (Roundabout homolog 2) is a member of the immunoglobulin superfamily and part of the ROBO receptor family, which is critical in the SLIT-ROBO signaling pathway. This receptor, characterized by extracellular immunoglobulin (Ig) and fibronectin type III (FNIII) domains, a transmembrane region, and an intracellular domain, mediates cellular migration, adhesion, and tissue remodeling during development and adulthood¹.

Robo2 is expressed in the nervous system, kidneys, pancreas, lungs, and retinal vasculature, contributing to organogenesis, angiogenesis, and immune modulation^2,3. Subcellularly, it localizes to the plasma membrane. In axonal guidance, SLIT2 binding activates Robo2, leading to cytoskeletal remodeling via Rho family GTPases, while in non-neuronal tissues, it engages TGF-β signaling to regulate mesenchymal activation and tissue fibrosis^3,4.

Dysregulation of Robo2 is implicated in several diseases. Mutations in ROBO2 are associated with congenital anomalies of the kidney and urinary tract (CAKUT), where disrupted SLIT-ROBO signaling impairs ureteric budding and nephric duct patterning^1,4. In the pancreas, ROBO2 acts as a stroma suppressor, limiting TGF-β-driven myofibroblast activation and immune cell infiltration in pancreatic ductal adenocarcinoma (PDAC)². In the retina, Robo2 promotes angiogenesis and vascular development, partly compensating for VEGF signaling³. Reduced expression of ROBO2 in PDAC and ocular diseases is correlated with poorer outcomes^2,3,5.

This receptor’s roles in axon guidance, organogenesis, and disease make it a significant target for therapeutic strategies, including inhibitors of SLIT-ROBO or TGF-β pathways^2,3,5.