MYO5B encodes myosin VB, a molecular motor protein essential for intracellular vesicular trafficking and membrane transport processes. The protein facilitates trafficking of key transporters including the bile salt export pump (BSEP/ABCB11) to the apical membrane of hepatocytes, which is critical for proper bile formation and secretion 1. MYO5B works in complex with RAB11 GTPases to transport various cargo proteins, including NPC1L1 for cholesterol absorption and supports epithelial cell polarization 2. The protein also mediates fibronectin secretion through RAB11b-dependent vesicular transport, contributing to extracellular matrix formation 3. Clinically, MYO5B mutations cause progressive familial intrahepatic cholestasis type 10 (PFIC10), characterized by impaired bile flow, cholestasis, and progressive liver disease 45. Interestingly, the clinical severity and treatment response in MYO5B-associated cholestasis do not correlate directly with BSEP localization abnormalities, suggesting multiple pathogenic mechanisms beyond BSEP trafficking defects 6. Recent clinical trials demonstrate that PFIC patients, including those with MYO5B variants, respond to maralixibat treatment, which reduces pruritus and serum bile acids by inhibiting intestinal bile acid reabsorption 7. This highlights the therapeutic potential of targeting bile acid homeostasis in MYO5B-related liver disease.