Rab21, a member of the Rab family of small GTPases, plays crucial roles in regulating intracellular transportation and cargo delivery. It is involved in multiple pathways such as endosomal sorting, autophagy, and glucose uptake, which are essential for maintaining cellular homeostasis [2].

Depletion of Rab21 in various models has revealed its significance. In cancer cells, RAB21 depletion mis-sorts SLC2A1 to lysosomes, affects glucose uptake, activates the AMPK-ULK1 pathway to increase autophagic flux, and sensitizes cells to energy stress, suggesting an oncogenic role [1]. In enterocytes, Rab21 depletion leads to intestinal morphology abnormalities, deregulated cellular equilibrium, and tissue inflammation, indicating its role in intestinal epithelium maintenance [3]. In neurons, Rab21 loss of function increases membrane-exposed APP levels, impairing cortical neuronal differentiation and migration [4].

In conclusion, Rab21 is essential for maintaining cellular functions in processes like autophagy, energy homeostasis, and tissue development. Studies using gene knockout or knockdown models have highlighted its significance in diseases such as cancer, neurodegenerative diseases, and intestinal disorders, providing potential therapeutic targets for these conditions.