biostudies-literatureUnknown28(11)Ma WThe kinase thousand and one amino acid kinase 2 (TAOK2) regulates dendritic architecture and synaptic plasticity and is implicated in neurodevelopmental and neuropsychiatric disorders, including autism and schizophrenia. Here, we investigated TAOK2 function by creating an <i>Emx1-Cre</i>-driven, excitatory-neuron-specific conditional <i>Taok2</i> knockout (<i>Taok2</i> cKO) mouse line. Pathway profiling in <i>Taok2</i> cKO primary cortical neurons revealed impaired extracellular regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and calcium signaling after AMPA, BDNF, or bicuculline stimulation. These results were validated by reduced p-ERK1/2 protein levels and decreased calcium flux. Cultured <i>Taok2</i> cKO neurons displayed reduced synaptic density and connectivity. SingleiScience113712https://www.ebi.ac.uk/biostudies/studies/S-EPMC12590003biostudies-literatureTAOK2 controls synaptic plasticity and anxiety via ERK and calcium signaling.PMC12590003Volkmann PRossner MJJensen NScheuss VStephan MDehne KMa XKannaiyan NWehr MCBrankatschk BWarnhoff IMa WfalseTAOK2 controls synaptic plasticity and anxiety via ERK and calcium signaling.The kinase thousand and one amino acid kinase 2 (TAOK2) regulates dendritic architecture and synaptic plasticity and is implicated in neurodevelopmental and neuropsychiatric disorders, including autism and schizophrenia. Here, we investigated TAOK2 function by creating an <i>Emx1-Cre</i>-driven, excitatory-neuron-specific conditional <i>Taok2</i> knockout (<i>Taok2</i> cKO) mouse line. Pathway profiling in <i>Taok2</i> cKO primary cortical neurons revealed impaired extracellular regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and calcium signaling after AMPA, BDNF, or bicuculline stimulation. These results were validated by reduced p-ERK1/2 protein levels and decreased calcium flux. Cultured <i>Taok2</i> cKO neurons displayed reduced synaptic density and connectivity. Single2025-01-01T00:00:00Z2025 Nov2026-06-05T13:45:42.05Z2026-06-05T03:06:56.531ZS-EPMC125900034121098410.1016/j.isci.2025.113712