A Young Child With Global Developmental Delay and Epilepsy Secondary to a Novel Variant of KBG Syndrome.

Extracellular vesicles (EVs) are heterogeneous membrane-limited particles released into the extracellular space by cells of endosomal or plasma membrane origin that have emerged as a major pathway of cell-cell communication across various biological contexts. Interest in EVs has expanded rapidly because they can carry membrane proteins, cytosolic proteins, lipids, RNAs, and metabolites, thereby transferring complex molecular information between cells. In mammals, EVs have been implicated in development, tissue repair, immune regulation, infection, cancer progression, and neurological disease, which are increasingly investigated as liquid-biopsy analytes and therapeutic delivery vehicles. At the same time, the field continues to face conceptual and technical challenges. EV preparations are heterogeneous, subtype definitions are not always experimentally established, and the biological significance of detected cargo cannot be assumed without functional validation. Accordingly, current consensus guidelines emphasize the precise use of terminology and the application of rigorous characterization approaches to clearly differentiate general claims about EVs from those pertaining to specific subtypes, such as exosomes or microvesicles. This is particularly important in cross-species studies, in which the strengths of different model systems enable complementary aspects of EV biology to be analyzed. Among model organisms, provides an excellent model system due to its ease of genetic manipulation and well-established tools for studying interorgan communication. combines powerful tissue-specific genetics with a high degree of conservation in membrane trafficking, endosomal sorting, and developmental signaling pathways. Together, these features make a valuable comparative model for defining conserved EV mechanisms and their physiological functions across tissues and organisms. In this review, we discuss current knowledge of EV nomenclature, biogenesis, cargo selection and biological function, with particular emphasis on the conserved and divergent features of mammalian and EV biology. We compare and mammalian EV biology with three aims. First, we review conserved mechanisms of cargo selection and vesicle release, with emphasis on the endosomal sorting complexes required for transport (ESCRT) machinery, Rab GTPases, tetraspanins, and lipids. Second, we compare the biological functions of EVs in mammalian physiology and disease with those described in development and neurobiology. Third, we evaluate the strengths and limitations of as a mechanistic model for mammalian EV research and translational EV biology. Finally, we highlight the need for further work to define how EV pathways operate across tissues and organisms, and emphasize how comparative studies in mammals and will advance both mechanistic insight and translational applications.