Abstract: Background: Failure of axon regeneration after spinal cord injury (SCI) underlies the paralysis that so profoundly affects patients’ quality of life.  Many factors are involved in the regeneration failure. Chondroitin sulfate proteoglycans (CSPGs), normal constituents of the perineuronal nets in central nervous system (CNS), are secreted at the injury site and initially were thought to act as a purely physical barrier. In the past decade, the receptor-like protein tyrosine phosphatases, protein tyrosine phosphatase sigma (PTPσ), and leukocyte common antigen-related phosphatase (LAR), have been identified as transmembrane receptors for CSPGs. The two receptors for myelin-associated growth inhibitors, Nogo receptors 1 and 3 (NgR1 and NgR3) also have been found to bind with CSPGs (Sharma et al., 2012). These findings suggest that CSPGs inhibit regeneration by interacting with these receptors, initiating downstream inhibitory signaling (Figure 1).