MARK1 is a serine/threonine-protein kinase that regulates microtubule dynamics and cellular polarity by phosphorylating microtubule-associated proteins including TAU, MAP2, and MAP4 at KXGS motifs, causing their detachment from microtubules 1. This phosphorylation activity is critical for neuronal migration and dendritic spine morphogenesis 2. MARK1 also functions as a positive regulator of Wnt signaling by phosphorylating dishevelled proteins 1. Loss of MARK1 in forebrain-specific conditional knockout mice causes defects in dendritic spine morphogenesis in hippocampal CA1 neurons with reduced spine density, and impairs spatial learning and anxiety-related behaviors, indicating essential roles in cognitive functions 2. In disease contexts, MARK1 participates in tau-related pathology; co-expression of MARK1 with human tau isoforms produces combinatorial toxicity in Drosophila nervous systems, potentially through direct tau phosphorylation 3. In hepatocellular carcinoma, MARK1 acts as a critical modulator of TGF-β resistance and epithelial-to-mesenchymal transition 4. Additionally, MARK1 is a functional target of miR-125a-5p, with inverse expression correlating to cervical cancer cell migration 5. The kinase's activity is regulated by autoinhibition through its C-terminal KA1 domain, which blocks substrate binding 6.