TBC1 domain family member 5

TBC1 domain family member 5 (TBC1D5) is a GTPase-activating protein that regulates Rab family GTPases, particularly RAB7A (UniProt: Q92609). It functions in retrograde cargo transport from endosomes to the trans-Golgi network and plays a key role in autophagy regulation by controlling vesicle trafficking between endosomal and autophagosomal compartments, including recruitment of ATG9A-containing vesicles to autophagic membranes.

TBC1D5 is involved in intracellular membrane trafficking and autophagosomal processes essential for neuronal homeostasis. No specific disease associations are documented in UniProt annotation.

TBC1D5 is upregulated in Alzheimer's disease brain tissue. Chaparral AD proteomics analysis of post-mortem AD brain compared to age-matched controls detected consistent upregulation across multiple subcellular fractions (4 fractions analyzed via TMT-labeled tandem mass spectrometry), with a mean log₂ fold-change of 0.38. This elevation may reflect altered autophagy or membrane trafficking responses in AD pathology.