SPN and autism spectrum disorder: In sharp contrast, two autism spectrum disorder-related SHANK3 variants (R12C and L68P) within the SPN domain that are unable to bind to Rap1–GTP (Lilja et al., 2017; Mameza et al., 2013) failed to block activation of Rap1 or αVβ3 in response to optogenetic recruitment of talin to the plasma membrane of endothelial cells (Fig. 3D,E).