SMAP2 (small ArfGAP2) is an Arf GTPase-activating protein that primarily functions as a regulator of Arf1-dependent membrane trafficking 1. The protein exhibits GAP activity toward Arf1 and localizes to both early endosomes and the trans-Golgi network (TGN), where it interacts with clathrin heavy chain and the clathrin assembly protein CALM 1. SMAP2 plays a critical role in retrograde transport from early endosomes to the TGN, as overexpression delays TGN38/46 accumulation on the TGN 1. At the TGN, SMAP2 functions as a negative regulator of vesicle budding, controlling the organized formation of clathrin-coated vesicles 23. The protein is essential for male fertility, as SMAP2-deficient mice exhibit globozoospermia due to impaired acrosome formation during spermiogenesis 3. SMAP2 physically associates with SMAP1 and can functionally compensate for SMAP1 in transferrin receptor endocytosis 4. Double knockout of both SMAP1 and SMAP2 results in embryonic lethality, indicating overlapping essential functions during development 5. Recent genetic studies have identified variants near SMAP2 associated with Alzheimer's disease risk 6.