Rab5a, a member of the Rab small GTPase family, is crucial for early endosome biogenesis, autophagy initiation, and vesicle trafficking [4]. It is involved in multiple cellular processes and signaling pathways, such as the IGF-AKT-mTOR signaling pathway during muscle regeneration, and its dysregulation is associated with various diseases [3]. Genetic models, like gene knockout (KO) mouse models, have been valuable in studying its functions.

In colonic epithelial cells, Rab5a is essential for cytolethal distending toxin B (CdtB)-induced cytotoxicity and apoptosis, as Rab5a silencing or knockout largely inhibits these effects. In THP-1 macrophages, Rab5a is required for CdtB-induced pro-inflammatory cytokine production and activation of NF-κB and JNK signaling [1]. In muscle regeneration, myogenic Rab5a-deficient mice show that Rab5a is essential for regulating skeletal muscle regeneration, as it promotes myoblast differentiation and activates IRS1 to coordinate IGF-AKT-mTOR signaling [3]. In Alzheimer's disease (AD) 5×FAD mice, Rab5a hyperactivation is an early pathological manifestation, and electroacupuncture can suppress Rab5a-GTP to promote NGF signaling transduction and improve cognitive impairment [2].

In conclusion, Rab5a is a key regulator in multiple biological processes. Model-based research, especially using KO mouse models, has revealed its role in diseases such as post-infectious irritable bowel syndrome, rheumatoid arthritis, AD, and muscle-related disorders. Understanding Rab5a's functions provides insights into disease mechanisms and potential therapeutic targets.