# Significant Association Between Glucokinase Regulatory Protein Variants and Genetic and Metabolic Diseases

## TL;DR

This paper reviews how variations in the GCKR gene are linked to metabolic diseases and suggests it could be a target for new treatments.

## Contribution

The paper systematically reviews the role of GCKR variants in metabolic diseases and highlights their potential as drug targets.

## Key findings

- GCKR variants are strongly associated with metabolic diseases like hypertriglyceridemia and NAFLD.
- A drug targeting the GCK-GKRP complex has shown preclinical effectiveness but may have side effects.
- Developing diverse drugs and conducting clinical trials could improve treatment outcomes for metabolic diseases.

## Abstract

As next-generation sequencing develops, there are significant associations between glucokinase regulatory protein (GCKR) variants and many diseases, especially metabolic diseases. However, there is a lack of solid descriptions and summaries of how GCKR variants lead to diseases and a lack of successful translations of drugs targeting this molecular variant. We searched literature datasets, mainly including PubMed and Web of Science, with “GCKR” or “GKRP”, “Variants”, “Hypertriglyceridemia”, “NAFLD”, and “Metabolic diseases” as the search terms. Our review firstly introduces the biological function of the GCKR gene and its encoding protein GKRP and then describes the GCKR variants in different diseases, such as hypertriglyceridemia and NAFLD, revealing that GCKR/GKPR is strongly associated with metabolic diseases. GKPR might be a potential target for T2D and other metabolic diseases. One drug for interfering with the GCK-GKRP complex has been developed and has shown its effectiveness in preclinical studies, with some possible side effects. More and more different-structured drugs should be developed to improve side effects, and more clinical trials should be carried out to determine the best intervention window and timing points to improve prognosis. Taken together, these insights show that GCKR/GKRP is significantly associated with many metabolic diseases via its complex metabolism system and is a potential target in many metabolic diseases.