MARK2, also known as Microtubule affinity-regulating kinase 2, is a serine/threonine protein kinase. It phosphorylates microtubule-associated proteins and is crucial in multiple biological processes. MARK2 regulates signaling pathways like WNT, PI3K/AKT/mTOR, and NF-κB, linking it to cancer and the nervous system [3].

In neurodevelopment, MARK2 variants (predominantly loss-of-function) in 31 individuals were associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. MARK2 loss in proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells led to early neuronal developmental and functional deficits. Mark2+/- mice showed abnormal cortical formation, partition, and ASD-like behavior, with MARK2 loss linked to down-regulation of the WNT/β-catenin signaling pathway [1]. In cancer, MARK2/3 were identified as catalytic codependencies of YAP/TAZ in human carcinoma and sarcoma. Inhibiting MARK2/3 can reactivate the Hippo tumor-suppressive pathway [2].

In conclusion, MARK2 is essential for neuronal development and is involved in cancer-related processes. Gene-knockout mouse models, such as Mark2+/- mice, have been instrumental in revealing its role in ASD-related neurodevelopmental disorders and cancer, providing insights into potential therapeutic targets for these diseases.