Rab37, a member of the RAS oncogene family, is a small GTPase that plays a crucial role in vesicle biogenesis, trafficking, and cargo release [1,2,7,8]. It is involved in multiple biological processes, including autophagy, insulin secretion, and the differentiation and function of various cell types. These functions are essential for maintaining normal physiological homeostasis and are associated with several disease-related pathways. Genetic models, especially gene knockout mouse models, have been valuable in studying Rab37's functions.

Conditional knockout of Rab37 in oocytes impairs autophagy proficiency in the ovary, interfering with follicular homeostasis and ovary development in mice, highlighting its role in maintaining ovarian function [1]. In pancreatic β-cells, the active form of Rab37 is essential for autophagy-promoted insulin secretion, as demonstrated in rab37 knockout cells and mice, emphasizing its importance in glucose homeostasis [2]. In adipose-derived mesenchymal stem cells (ADSCs), Rab37 promotes endothelial differentiation and accelerates ADSC-mediated diabetic wound healing, and in human adipose-derived mesenchymal stem cells (hADSCs), it positively regulates adipogenic differentiation [3,4]. In the context of cancer, in M2 macrophages, Rab37 mediates ST2L trafficking to the plasma membrane, promoting a positive-feedback loop that limits chemotherapeutic efficacy in lung cancer [5]. In T cells, Rab37 mediates trafficking and membrane presentation of PD-1 to sustain T-cell exhaustion in lung cancer [6].

In conclusion, Rab37 is essential for multiple biological processes such as autophagy, cell differentiation, and secretion. The use of KO/CKO mouse models has revealed its significance in diseases related to ovarian function, metabolic regulation, and cancer progression. Understanding Rab37's functions provides insights into the underlying mechanisms of these biological processes and diseases, potentially offering new directions for therapeutic interventions.