G6pc1, or glucose-6-phosphatase catalytic subunit 1, is crucial for glucose homeostasis as it catalyzes the final rate-limiting step in endogenous glucose production, participating in pathways like gluconeogenesis and glycogenolysis [2,3,6]. This membrane-integrated enzyme, along with accessory transport proteins, hydrolyzes glucose-6-phosphate (G6P) to glucose in the endoplasmic reticulum lumen [1,6,7]. Dysregulation of G6pc1 is associated with diabetes and glycogen storage disease type 1a [3,6,7]. Genetic models, such as mouse models, are valuable for studying its function.

In a humanized mouse model (huR83C) for glycogen storage disease type-Ia, lacking blood glucose control due to a deficient G6PC1 gene, base-editing was able to correct the G6PC1-R83C variant. This restored blood glucose control, improved metabolic abnormalities, and conferred long-term survival, showing that G6pc1 is essential for proper glucose regulation in this disease context [4]. In German Pinschers with glycogen storage disease type Ia (GSD1A), a polyadenine insertion disrupting the G6PC1 gene was identified [5].

In conclusion, G6pc1 is fundamental for maintaining glucose homeostasis through its role in key glucose-related metabolic pathways. Studies using gene-deficient mouse models and other animal models have revealed its critical importance in diseases like glycogen storage disease type 1a. Understanding G6pc1 function provides insights into the mechanisms of glucose-related disorders, potentially guiding the development of therapeutic strategies for such diseases.