MARK2 is a serine/threonine protein kinase that regulates microtubule dynamics and cell polarity through phosphorylation of microtubule-associated proteins including tau, MAP2, and MAP4 1. The kinase plays essential roles in neuronal development by regulating axogenesis, neurite outgrowth, and dendritic spine development, partly through phosphorylation of dishevelled proteins in Wnt/β-catenin signaling 2. MARK2 also modulates epithelial cell polarity and ER homeostasis by phosphorylating RAB11FIP2 and UBAC2, respectively 3. Clinically, MARK2 loss-of-function variants are associated with autism spectrum disorder and neurodevelopmental disorders, identified as a moderate-risk gene affecting 95 individuals with less cognitive impairment than highly penetrant variants 42. Loss of MARK2 in patient-derived neurons leads to abnormal neural polarity, neural rosette disorganization, and imbalanced neuronal progenitor proliferation, with lithium treatment potentially restoring WNT/β-catenin signaling 2. Additionally, MARK2 functions as a catalytic codependency of YAP/TAZ oncoproteins in cancer by phosphorylating NF2 and YAP/TAZ, representing a therapeutic vulnerability in YAP/TAZ-dysregulated carcinomas and sarcomas 5. MARK2 also regulates the PI3K/AKT/mTOR pathway and tau phosphorylation, connecting it to cancer progression and neurodegeneration 6.