ANKRD27 (ankyrin repeat domain 27), also known as VARP (VPS9-ankyrin-repeat protein), is a multifunctional regulator of endosomal trafficking 1. As a guanine exchange factor (GEF), ANKRD27 activates small GTPases Rab21, Rab32, and Rab38 to coordinate endosome dynamics and vesicular transport 1. ANKRD27 interacts with the retromer complex through Zn-fingernail domains that bind VPS29, enabling endosome-to-plasma-membrane recycling of cargo proteins including GLUT1 2. The protein regulates VAMP7 function by trapping it in an inactive conformation, thereby controlling SNARE-mediated membrane fusion events 1. In melanocytes, ANKRD27 coordinates trafficking of melanogenic enzymes (TYR, TYRP1, DCT/TYRP2) to melanosomes through cooperation with Rab32, Rab38, and VAMP7 3. ANKRD27 also promotes neurite outgrowth, requiring its GEF activity toward Rab21 and VAMP7 1. Disease relevance includes association with eosinophilic esophagitis, a chr19 allergic inflammatory disorder of the esophagus 4, and potential susceptibility to SARS-CoV-2 infection 5. The protein's pleiotropic functions in membrane trafficking make it a candidate therapeutic target for inflammatory and infectious diseases.