AbstractThe inability to specifically identify and manipulate synaptic glial cells remains a major obstacle to understanding fundamental aspects of synapse formation, stability and repair. Using a combinatorial gene expression approach, we discovered molecular markers that allow us to specifically label perisynaptic Schwann cells (PSCs), glial cells at neuromuscular synapses. Using these markers, we demonstrate that PSCs fully-differentiate postnatally and have a unique molecular signature that includes genes predicted and known to play critical roles at synapses. These findings will serve as a springboard for unprecedented approaches for studying molecular determinants of PSC differentiation and function at neuromuscular synapses and possibly synapse-associated glia throughout the CNS.