Neuronal functions of CYFIP2 and potential effects of the Arg87 variants identified in the West syndrome on those functions. (A) The Arg87 variants weaken the inhibitory CYFIP2-VCA interaction, thereby leading to aberrant activation of WRC and the downstream actin polymerization. This may result in dendritic spine remodeling and change excitatory/inhibitory synaptic balance, in favor of more excitation. (B) Similar to CYFIP1, CYFIP2 may also regulate neurotransmitter release in the presynaptic compartment, and the Arg87 variants may affect this function of CYFIP2. (C) The WRC interacts with certain ion channels potentially involved in regulating neuronal excitability. Given that CYFIP and ABI of the WRC form an interaction surface toward those membrane proteins, the Arg87 variants may indirectly affect such interactions, thereby changing surface stability or other functional properties of ion channels. (D) In addition to the WRC, CYFIP2 also interacts with some mRNA-binding proteins, such as FMRP, to regulate target mRNA transport and local translation. The Arg87 variants may affect formation of these mRNA-regulatory protein complexes, or their function in regulating target mRNAs.