Rab27a, a small GTPase, is a crucial regulator in multiple membrane-trafficking processes. It exists in an 'active' GTP-bound and 'inactive' GDP-bound state, acting as a molecular switch. It is involved in pathways such as exosome secretion, insulin secretion, and vesicular trafficking in various cell types, which are vital for intercellular communication, metabolism, and immune response [3,4,7]. Genetic models, like KO mouse models, are valuable for studying its functions in vivo.

In exosome secretion, RNA interference (RNAi) screening in HeLa cells showed that Rab27a functions in multivesicular endosome (MVE) docking at the plasma membrane, and its silencing strongly increased MVE size [1]. In pancreatic β-cells, Rab27a regulates pre-exocytotic stages of insulin secretion via GTP-specific effectors, and its GDP-bound form interacts with GDP-specific effectors to control endocytosis, synchronizing with secretory membrane recycling [4]. In neurons and podocytes, knockdown of KIBRA, which stabilizes Rab27a, decreased exosome secretion, while overexpression increased it [2]. In colon cancer cells, RAB27A knockdown inhibited proliferation, clone formation, migration, and invasion, indicating its role as an onco-protein in colorectal cancer development [5]. In cerebral ischemic injury, Rab27a knockout mice had decreased brain exosome levels, increased infarct volume, and neurological deficit scores, while pre-infusion of exosomes from wild-type mice improved the situation [6].

In conclusion, Rab27a is essential for membrane-trafficking related biological functions such as exosome secretion, insulin secretion, and vesicular trafficking. Model-based research, especially Rab27a KO mouse models, has revealed its significance in diseases like colorectal cancer and cerebral ischemic injury, providing insights into disease mechanisms and potential therapeutic targets.