TBC1D22B is a GTPase-activating protein (GAP) that regulates membrane trafficking and cellular metabolism with emerging roles in cancer. Functionally, TBC1D22B acts as a RAB-family GAP, specifically inactivating RAB1B to inhibit ER-to-Golgi transport 1. It also participates in tubular endosome formation through GAP-activity-dependent mechanisms 2. Beyond canonical trafficking functions, TBC1D22B interacts with ACBD3 at the Golgi apparatus, where it competes with phosphatidylinositol 4-kinase recruitment, potentially regulating lipid signaling 3. Clinically, TBC1D22B overexpression associates with poor prognosis in breast cancer, particularly triple-negative breast cancer, where it drives a glycolytic metabolic phenotype 4. In breast cancer cells, TBC1D22B promotes oncogenic programs through its GAP-dependent inhibition of ER-to-Golgi trafficking, leading to repression of extracellular matrix and adhesion genes that facilitate tumor growth 1. Additionally, TBC1D22B hypomethylation at specific CpG sites associates with increased risk of venous thromboembolism recurrence in men, suggesting broader vascular implications 5. These findings establish TBC1D22B as a multifunctional membrane trafficking regulator with significant implications for cancer progression and thrombotic disease risk.