Figure 1.

(a) Structural differences among ROBO4 and other ROBOs, (b) Proposed mechanism of soluble ROBO4 to inhibit pathological angiogenesis: SLITs maintain vessel integrity via ROBO1–ROBO4. ROBO1 has more efficient binding with SLIT2 than ROBO4. After SLIT2-ROBO1 binding, deficiency of free SLIT2 triggers the soluble ROBO4 self-multimerization and/or ROBO1–ROBO4 heterodimerization which enhances the SLIT2-ROBO1 signalling promoting the vascular integrity. On the other hand, soluble ROBO4 interacting with UNC5B maintains the vessel integrity by counteracting the VEGF pathway.