Rab5C, a member of the Rab GTPase family, plays a crucial role in intracellular vesicular trafficking, specifically in the endocytic pathway, membrane protein recycling, and signaling [1]. These functions are vital for maintaining normal cellular activities and are involved in various biological processes. Genetic models such as those in C. elegans, zebrafish embryos, and cell lines have been valuable in studying Rab5C.

In humans, missense variants in RAB5C can lead to macrocephaly and mild-to-moderate developmental delay. In vitro and in vivo studies, including those in C. elegans and zebrafish, confirm these variants are damaging, disrupting the endocytic pathway [1]. In rectal cancer, Rab5C enhances resistance to ionizing radiation by modulating EGFR internalization, affecting DNA repair proteins Ku70 and Ku80 [2]. In breast cancer, HuR promotes cell survival by facilitating RAB5C expression, suggesting RAB5C functions as an oncogene [3]. In zebrafish, Rab5c is essential for hematopoietic stem and progenitor cell (HSPC) specification through endocytic trafficking of Notch and AKT signaling [4]. In respiratory epithelial cells, Rab5c promotes RSV and ADV replication via autophagy [5]. In male ankylosing spondylitis, RAB5C may play a role in the disease through regulating immune cell functions [6]. In thyroid papillary carcinoma cells, miR-145 inhibits cell proliferation and invasion by down-regulating rab5c [7]. In colorectal cancer, lncRNA BCAR4 promotes oxaliplatin resistance by modulating miR-484-3p/RAB5C expression [8]. During angiogenesis, the RIN2/Rab5C machinery prevents VEGFR2 degradation to control gene expression and tip cell identity [9].

In conclusion, Rab5C is essential for multiple biological processes including endocytic trafficking, cell development, and various disease-related mechanisms. Model-based research, especially in non-mouse models like C. elegans and zebrafish, has provided significant insights into the role of Rab5C in diseases such as neurodevelopmental disorders, cancers, and viral infections. These findings contribute to a better understanding of the underlying biological mechanisms and may potentially lead to new therapeutic strategies.