TBC1D3 is a hominoid-specific gene family that acts as a GTPase activating protein for RAB5 and plays critical roles in neuronal development and cellular signaling. The gene has undergone extensive duplication during primate evolution, with humans showing high copy number variation (up to 20 copies) clustered on chromosome 17 1. In cortical development, TBC1D3 promotes the generation of outer radial glial cells and basal neural progenitors, contributing to cortical expansion and folding characteristic of primate brains 2. The protein regulates synaptic maturation timing through interaction with MICAL1, promoting dendritic arborization early in development while later translocating to the nucleus to suppress synaptic maturation genes via chr17 remodeling 3. TBC1D3 also modulates insulin/IGF-1 signaling by preventing IRS-1 degradation through PP2A activation and p70 S6 kinase suppression 4. Additionally, it promotes cancer cell migration by enhancing MMP-9 expression, with its stability regulated by calmodulin-mediated protection from ubiquitination 5. The protein exhibits high intrinsic disorder, facilitating protein-protein interactions and post-translational modifications 6.