RASEF, also known as Rab45, is an atypical Rab GTPase. It contains N-terminal EF-hand and coiled-coil domains, along with a C-terminal Rab-GTPase domain. It functions as a key regulator in membrane trafficking, and has been associated with processes like DNA repair, and may play important roles in various biological and disease-related pathways [2,7]. Genetic models, such as knockout mice, are valuable for studying its functions in vivo.

In pancreatic acinar cells, RASEF-knockout (KO) mice studies revealed that RASEF likely regulates the formation and sorting of zymogen granules and secretion of digestive enzymes. Pancreatic acinar cells in RASEF-KO mice had an increased number of zymogen granules, abnormal organelle formations, and impaired enzyme release upon cerulein administration [2].

In the context of diseases, in colorectal cancer, high RASEF expression was associated with a better prognosis, and it may act as a suppressor gene, potentially inhibiting cancer development through participation in DNA repair processes [1]. In breast cancer, RASEF mRNA expression levels were associated with hormone receptor status, with lower expression in patients with negative hormone receptor status [3]. In pulmonary hypertension rats, cigarette smoke-induced RASEF hypermethylation led to pulmonary arterial smooth muscle remodeling, and RASEF overexpression inhibited this remodeling [4]. In lung cancer, elevated RASEF promoted cell growth via enhanced ERK signaling and was associated with poor prognosis [5]. In uveal melanoma, low RASEF expression correlated with promoter methylation and was associated with decreased survival, suggesting a tumor-suppressor role [6].

In conclusion, RASEF plays essential roles in multiple biological processes, including membrane trafficking in pancreatic acinar cells. Its functions in disease are diverse, with implications in cancer prognosis and development, as well as in pulmonary arterial remodeling. Studies using RASEF KO mouse models have provided valuable insights into its role in these specific disease areas.