It is difficult for regeneration of central nervous system (CNS) in adult mammals, and myelin-associated inhibitors (MAIs) are believed to be major contributors. Paired immunoglobulin-like receptor B (PirB), as a co-receptor of MAIs, and expresses highly in CNS after injury, plays a vital role in the signal transduction of inhibition in the injured CNS. Knockout or block of PirB in vitro and in vivo may promote the neuro-regeneration after spinal cord injury or hypoxic-ischemic brain damage, release the damage induced by β-amyloid in Alzheimer's disease, recover the neural function in brain inflammation models, improve the reconstruction of vision after optic nerve injury, and so on. PirB may be a potential therapeutic target for neuro-regeneration and synaptic plasticity.