The C-terminal domain of NLG1 is sufficient to enhance spine and synapse number and to modulate synaptic plasticity, and it exerts these effects via its interaction with SPAR and the subsequent activation of LIMK1/cofilin-mediated actin reorganization.

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Highlights d Activity blockade by TTX induces rapid and transient release of NGPF2 d NGPF2 is necessary and sufficient for synaptic scaling up d NGPF2 triggers synaptic scaling up through ALK-LIMKcofilin pathway d NGPF2 synthesis requires FMRP1

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