Rab6a, a member of the RAB GTPase family, plays a crucial role in intracellular vesicular transport, including retrograde trafficking [2,5,6]. It is involved in the targeted transport of neurotrophic receptors and inflammatory cytokines, and its mediated secretory pathway participates in numerous physiological and pathological processes [1]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been valuable in studying Rab6a's functions.

In cholangiocarcinoma, knockdown of Rab6a impedes cancer stem cells properties, epithelial-mesenchymal transition in vitro, and tumor growth in vivo. It binds to OPN, a target cargo, and affects OPN secretion and the AKT signaling pathway, suggesting targeting the RAB6A/OPN axis could be a therapy strategy [1]. In the context of human papillomavirus (HPV) entry, Rab6a knockdown impairs HPV exit from the trans-Golgi network (TGN) and intra-Golgi transport, as it facilitates HPV association with dynein and BICD2 in the TGN [2]. In pulmonary artery smooth muscle cells under hypoxia, Rab6a is induced by hypoxia and is involved in hypoxia-induced phenotypic switch and endoplasmic reticulum stress [3]. Loss of Rab6a in the small intestine of mice (Rab6a∆IEC mice) causes lipid accumulation and epithelial cell death from lactation, indicating its role in regulating lipid transport and tissue integrity [4]. In mouse oocytes, Rab6a knockdown leads to meiotic arrest at metaphase I, with defects in chromosome alignment, spindle organization, and increased aneuploidy incidence [7].

In conclusion, Rab6a is essential for multiple biological processes, including vesicular transport, cell phenotype modulation, and disease-related pathways. Studies using KO/CKO mouse models have revealed its significant roles in diseases such as cholangiocarcinoma, and have provided insights into potential therapeutic targets.