RAB8B is a small GTPase that regulates intracellular membrane trafficking by cycling between inactive GDP-bound and active GTP-bound forms to recruit effector proteins responsible for vesicle formation, movement, and fusion. 1 RAB8B plays a key role in autophagosome maturation during autophagy. 2 RAB8B is essential for Wnt/β-catenin signaling, mediating caveolin-dependent endocytosis and activity of the LRP6 coreceptor, with conservation across vertebrate species including Xenopus and zebrafish. 3 RAB8B regulates transport of West Nile Virus particles from recycling endosomes to the plasma membrane, with WNV infection enhancing its expression. 4 RAB8B interacts with optineurin (OPTN) through distinct molecular surfaces to regulate selective autophagy and ATG9A vesicle recruitment. 5 RAB8B serves as a substrate for the guanine nucleotide exchange factor DENN/MADD; mutations disrupting this interaction associate with neurodevelopmental disorders. 6 RAB8B expression is upregulated in schizophrenic patients, with the rs1986112 polymorphism correlating with increased expression levels. 7 RAB8B emerges as a potential therapeutic target for endometriosis and recurrent pregnancy loss. These findings establish RAB8B as a multifunctional regulator of vesicular trafficking with implications in development, viral pathogenesis, and psychiatric and reproductive disorders.