TAOK2, also known as Thousand and One Amino Acid Kinase 2, is a serine/threonine kinase. It is involved in multiple important biological functions. TAOK2 associates with the translational machinery and acts as a translational brake by phosphorylating eukaryotic elongation factor 2 (eEF2), revealing an eEF2K-independent signaling pathway for translation elongation control [1]. It also localizes in distinct ER subdomains and mediates the tethering of the endoplasmic reticulum (ER) to microtubules, regulating ER-MT coupling and cell division [2].

In Taok2 knockout mouse models, various phenotypes related to neurodevelopmental disorders are observed. Taok2-deficient mice show gene dosage-dependent impairments in cognition, anxiety, and social interaction, along with brain size and neural connectivity abnormalities, cortical layering deficits, and reduced excitatory neurotransmission [5]. Taok2 knockout also leads to unstable microtubules in neurons, disrupting neuronal migration [4]. In rats, spinal TAOK2 activation contributes to neuropathic pain via cGAS-STING signaling activation, as shown by the reversal of hyperalgesia after TAOK2 silencing [3].

In conclusion, TAOK2 plays essential roles in translation regulation, ER-MT tethering, and is crucial for normal neurodevelopment. The Taok2 knockout models have been instrumental in revealing its contributions to neurodevelopmental disorders like autism spectrum disorders and neuropathic pain, providing valuable insights into the underlying molecular mechanisms and potential therapeutic targets.