Rab7, a member of the RAS oncogene family, is a small GTPase that plays a crucial role in regulating endomembrane trafficking pathways, especially those related to endocytic and autophagic processes [4]. It cycles between an active GTP-bound state and an inactive GDP-bound state, interacting with various effector proteins to control multiple cellular functions [1,6].

Endothelial haploinsufficiency of Rab7 in mice led to spontaneous pulmonary hypertension (PH), as Rab7-silenced endothelial cells showed impaired angiogenesis, senescent cell expansion, and disrupted endolysosomal trafficking, suggesting a key role in maintaining endothelial function and lung vascular homeostasis [2]. In oocytes, the activity of Rab7 is essential for the regulation of mitophagy during meiosis and oocyte quality control in ovarian aging. When its activity was decreased in CCCP-treated oocytes, defects in meiosis and mitophagy occurred, which could be rescued by active Rab7 or its activator [3]. In diabetic cardiomyopathy, Rab7-Rilp-mediated microlipophagy may be a potential target for treating lipid toxicity, as treating DbCM mice with the Rab7 activator ML-098 enhanced Rilp level and rescued cardiac dysfunction [5].

In conclusion, Rab7 is a vital regulator in multiple biological processes, including endomembrane trafficking, mitophagy, and endothelial function. Gene-knockout models, such as Rab7-silenced endothelial cells and Rab7 haploinsufficient mice, have provided valuable insights into its role in diseases like pulmonary hypertension, oocyte-related disorders, and diabetic cardiomyopathy, highlighting its potential as a therapeutic target.