SLIT2 and both its natural cleavage products bind glypican-1 (GPC1), a glycosyl phosphatidyl inositol (GPI) anchored heparan sulfate proteoglycan (HSPG), through its C-terminus. Besides glypican-1, other HSPG may also be involved in SLIT2 binding. GPC1:HSPG is important for high affinity binding of SLIT to its receptor and for the repulsive activity of SLIT. SLIT-ROBO signaling strictly requires binding to heparan sulfate. HSPGs may also modulate the extracellular distribution or stability of SLIT proteins (Ronca et al. 2001, Zhang et al. 2004).