TBC1D9B is a GTPase-activating protein (GAP) that negatively regulates small Rab GTPases, primarily Rab11a and Rab8a, to control vesicular trafficking and organellar dynamics. The protein contains a conserved TBC (Tre2-Bub2-Cdc16) domain that directly binds GTP-loaded Rab proteins and stimulates their GTPase activity, converting them to inactive GDP-bound forms 1. TBC1D9B localizes to recycling endosomes and associates with the lysosomal membrane protein TMEM55B, which serves as a central hub for adaptor assembly 23. Beyond endosomal trafficking, TBC1D9B positively regulates autophagic flux through direct interaction with LC3B and other mammalian ATG8 homologues via a unique LC3-interacting domain, facilitating proper autophagosome maturation 4. TBC1D9B functions downstream of LMTK1 kinase in a signaling cascade (Cdk5-LMTK1-TBC1D9B-Rab11A) that regulates dendritic spine formation and synaptic development 5. Loss of TBC1D9B causes lysosome dispersion, defective autophagic flux, and impaired adaptive nutrient responses 2. Dysregulation of TBC1D9B has been implicated in Alzheimer's disease pathology 6 and identified as a hub gene in moyamoya disease angiogenesis dysfunction 7, suggesting therapeutic relevance in neurodegenerative and cerebrovascular disorders.