Strikingly, loss-of-function mutations in the human Nlgn4 ortholog NLGN4X cause autism spectrum disorder (ASD) in humans (Jamain et al., 2003; Yan et al., 2005; Kopp et al., 2021), and Nlgn4 knock-out (KO) mice exhibit ASD-like traits (Jamain et al., 2008; El-Kordi et al., 2013; Ju et al., 2014), establishing Nlgn4 KO mice as construct-valid and face-valid ASD models that can yield important insights into the pathomechanisms of ASD. This evidence concerns the gene NLGN4X and autism spectrum disorder.