MTM1 encodes myotubularin, an endosomal lipid phosphatase that dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) 1. The enzyme regulates endosome-mediated trafficking and negatively controls EGFR degradation through regulation of trafficking from late endosomes to lysosomes. MTM1 is essential for skeletal muscle maintenance, regulating desmin intermediate filament assembly, mitochondrial morphology, and positioning 2. In muscle tissue, MTM1 stabilizes MTMR12 protein levels and is required for proper T-tubule remodeling and excitation-contraction coupling. MTM1 mutations cause X-linked myotubular myopathy (XLMTM), a severe congenital disorder characterized by profound muscle weakness, central nuclei, myofiber hypotrophy, and organelle disorganization 1. Beyond muscle pathology, MTM1 loss causes cholestatic liver disease through impaired hepatocyte endosomal trafficking and bile canalicular transporter localization 3. Clinically, XLMTM presents with hypotonia and weakness from birth, often requiring ventilator and wheelchair dependence 1. Recent advances in AAV8-mediated MTM1 gene replacement therapy show promise, with treated patients achieving ventilator independence and improved motor function; however, hepatobiliary complications requiring careful monitoring have emerged 4. Therapeutic targeting of dynamin 2, a common pathway dysregulated in centronuclear myopathies, represents an alternative strategy under investigation 2.