Introduction: Neonatal seizures are common and phenobarbital has limited efficacy , creating a need for targets with better neurodevelopmental safety . ZDHHC14 is a palmitoyl acyltransferase that regulates PSD93/Kv1 channel clustering and neuronal excitability . Objectives: To test whether ZDHHC14 overexpression reduces cortical pyramidal neuron excitability in an Mg²? -freein vitro seizure model and in Kcnt1-269 mutant rats modelling human KCNT1 p.G288S developmental and epileptic encephalopathy . Methods: Neonatal Sprague–Dawley rats (