TBC1D5 (TBC1 domain family member 5) functions as a GTPase-activating protein (GAP) that regulates cellular trafficking and autophagy by modulating Rab7 activity 1. The protein plays a critical role in autophagy regulation by controlling the fusion of autophagosomes with lysosomes through its interaction with Rab7 2. TBC1D5 acts as a key regulator of ATG9 trafficking during autophagy initiation, associating with the AP2 complex and ULK1 complex to direct ATG9-containing vesicles toward autophagosome formation sites 3. The protein coordinates with the retromer complex to control endosomal trafficking, with its catalytic activity being essential for displacing both RAB7A and retromer from endosomal membranes 4. In synaptic development, TBC1D5 constrains synaptic growth by negatively regulating BMP signaling through modulation of Wit receptor levels 5. The protein's function extends to mitophagy regulation, where decreased TBC1D5 expression enhances Rab7 activity and improves mitochondrial clearance in Alzheimer's disease models 2. TBC1D5 also plays roles in oocyte development through regulation of mitophagic flux and can be targeted by viral proteins like SARS-CoV-2 ORF3a, which sequesters TBC1D5 to disrupt normal lysosomal function 6.