SLK (STE20-like kinase) is a serine/threonine kinase that plays critical roles in cytoskeletal organization and neuronal development. The protein regulates microtubule polarity and is essential for proper neuronal cell polarization, dendritic arborization, and synapse maturation 1. SLK mediates these functions through its involvement in actin stress fiber dissolution and focal adhesion regulation, contributing to cell migration and morphological plasticity. Mechanistically, SLK phosphorylates downstream targets to coordinate cytoskeletal dynamics. Recent evidence demonstrates that SLK-mediated S716 phosphorylation of USP8 is required for USP8 interaction with O-GlcNAc transferase (OGT), a regulatory interaction relevant to ferroptosis pathways in hepatocellular carcinoma 2. Clinically, biallelic SLK variants cause autosomal recessive neurodevelopmental disorder (NDD) characterized by impaired neuronal maturation, abnormal cytoskeletal organization, and reduced dendritic complexity 1. Patient-derived cells and Drosophila models of Slik deficiency recapitulate these phenotypes, confirming that cytoskeleton-mediated neuronal dysfunction underlies disease pathogenesis. SLK was also identified as a novel candidate gene in a broader study of intellectual disability etiology 3. These findings establish SLK as essential for proper neuronal development and identify cytoskeletal dysfunction as the primary mechanism of SLK-related disease.