The small GTPase Rab27 a is a member of the Rab family that is involved in membrane trafficking in various kinds of cells.Rab27 a has GTP-and GDP-bound forms,and their interconversion regulates intracellular signaling pathways.Typically,only a GTP-bound GTPase binds its specific effectors with the resulting downstream signals controlling specific cellular functions.We previously identified novel Rab27a-interacting proteins.Surprisingly,some of these proteins interacted with GDP-bound Rab27 a.The present study reviews recent progress in our understanding of the roles of Rab27 a and its effectors in the secretory process.In pancreatic β-cells,GTP-bound Rab27 a regulates insulin secretion at the preexocytotic stages via its GTP-specific effectors such as Exophilin8/Slac2-c/My RIP and Slp4/Granuphilin.Glucose stimulation causes insulin exocytosis.Glucose stimulation also converts Rab27 a from its GTP-to its GDP-bound form.GDP-bound Rab27 a interacts with GDP-specific effectors and controls endocytosis of the secretory membrane.Thus,Rab27 a cycling between GTP-and GDP-bound forms synchronizes with the recycling of secretory membrane to re-use the membrane and keep the β-cell volume constant. The small GTPase Rab27 a is a member of the Rab family that is involved in membrane trafficking in various kinds of cells. Rab27 a has GTP-and GDP-bound forms, and their interconversion regulates intracellular signaling pathways.Typically, only a GTP-bound GTPase binds its specific effectors with the resulting targeted signals specific cellular functions. We previously identified novel Rab27a-interacting proteins. Surprisingly, some of these proteins interacted with GDP-bound Rab27 a. The present study reviews recent progress in our understanding of the roles of Rab27 a and its effectors in the secretory process. In pancreatic beta-cells, GTP-bound Rab27 a regulates insulin secretion at the preexocytotic stages its its GTP-specific effectors such as Exophilin8 / Slac2-c / My RIP and Slp4 / Granuphilin. Glucose stimulation causes insulin exocytosis. Glucose stimulation also converts Rab27 a from its GTP-to its GDP-bound form. GDP-bound Rab27 a interacts with GDP-specific effectsors and control s endocytosis of the secretory membrane .hus, Rab27 a cycling between GTP-and GDP-bound forms synchronizes with the recycling of secretory membrane to re-use the membrane and keep the beta-cell volume constant.