TBC1D17 is a Rab GTPase-activating protein that functions as a key regulator of vesicular trafficking and autophagy. It inhibits Rab8A/B function by reducing Rab8 recruitment to tubules from the endocytic recycling compartment and suppressing Rab8-mediated endocytic trafficking, including transferrin receptor recycling 1. Additionally, TBC1D17 acts as a GAP for Rab5, regulating glucose transporter (Glut1/Glut4) translocation and glucose uptake through an AMPK-dependent mechanism where AMPK phosphorylation of TBC1D17 at Ser168 enhances its auto-inhibition 2. TBC1D17 localizes to autophagosomes and inhibits autophagy flux in a catalytically-dependent manner 3. Mechanistically, TBC1D17 interacts with optineurin (OPTN) and active Rab8a to form ternary complexes that facilitate Rab inactivation 4. Under hypoxia, SUMOylated FIS1 interacts with TBC1D17 to suppress hypoxia-induced mitophagy 5. Dysregulation of TBC1D17 is implicated in glaucoma pathogenesis through impaired autophagy 67 and associated with vitiligo and myasthenia gravis through altered mitophagy and immune regulation 89. TBC1D17 thus represents a critical hub integrating metabolic, trafficking, and autophagic pathways relevant to multiple human diseases.