For synaptic CAMs to exert biological effects in neurons, signals generated by their physical and chemical attachment must be intracellularly transduced to each compartment. Major scaffolding proteins have been identified and shown to interact with synaptic CAMs; for example, the important post-synaptic density protein PSD-95 interacts with neuroligins, LRRTMs, netrin-G ligands, SALMs (synaptic cell adhesion-like molecules) and Slitrk2 (Lim et al., 2022; Han et al., 2019). However, it remains unclear how signals generated by the unique pairings of synaptic adhesion molecules affect intracellular signal transduction pathways; clarifying this issue is crucial for understanding how synaptic CAMs act independently and collaboratively to maintain/regulate the structure and function of synapses. Intriguingly, a recent study pointed to the significance of multifaceted and multistage kinase networks in organizing synapse formation and compartmentalized postsynaptic cAMP signaling in regulating excitatory synaptic assembly. The CSDS is interested in using CRISPR-mediated genome-wide screens in vivo to identify a subset of synaptic CAMs that controls activation of certain protein kinase(s), with the goal of deciphering the detailed flow of intracellular signals in neurons.