Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (9): 4233-4234.doi: 10.4103/NRR.NRR-D-25-00967

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Rab5 hyperactivation: The central hub for endolysosomal dysfunction in Down syndrome

Xu-Qiao Chen*   

  1. Department of Neurosciences, University of California San Diego, La Jolla, CA, USA
  • Online:2026-09-15 Published:2026-05-11
  • Contact: Xu-Qiao Chen, PhD, q0chen@ucsd.edu.

Abstract: Rab5 as a central regulator of the endolysosomal network: The endolysosomal network (ELN) comprises a dynamic system of membranebound organelles responsible for cargo trafficking, degradation, and intracellular signaling, all of which are essential for maintaining cellular homeostasis. Within this system, members of the Rab family of small GTPases serve as key regulators of vesicular transport, marking specific compartments. Among them, Rab5 plays a pivotal role in orchestrating the formation of the early endosome (EE), membrane fusion events, and the transition of EE to downstream stages. Like other Rab proteins, Rab5 cycles between an active GTP-bound state and an inactive GDPbound state. This cycle is tightly controlled by guanine nucleotide exchange factors, which activate Rab5 by facilitating GDP-GTP exchange, and GTPase-activating proteins, which inactivate it by promoting GTP hydrolysis.