Functional studies demonstrate that Gαi1/3 are essential in mediating NLGN3-induced glioma cell progression in vitro and orthotopic primary glioma xenograft growth in vivo.NLGN3-stimulated glioma cell growth, proliferation and migration were largely inhibited by Gαi1/3 silencing, but enhanced by ectopic Gαi1/3 overexpression. Here, NLGN3 is linked to central nervous system cancer.