The role of ABCG2 in health and disease: Linking cancer therapy resistance and other disorders

All biological systems have adenosine triphosphate (ATP) binding cassette (ABC) transporters, one of the significant protein superfamilies involved in transport across membranes. ABC transporters have been implicated in the etiology of diseases like metabolic disorders, cancer, and Alzheimer's disease. ATP-binding cassette superfamily G member 2 (ABCG2), one of the ABC transporters, is necessary for the ATP-dependent efflux of several endogenous and exogenous substances. Consequently, it maintained cellular homeostasis and shielded tissue from xenobiotic substances. ABCG2 was initially identified in an Adriamycin-selected breast cancer cell line (MCF-7/AdrVp) and was linked to the emergence of multidrug resistance (MDR) in cancerous cells. Under many pathophysiological conditions, including inflammation, disease pathology, tissue injury, infection, and in response to xenobiotics and endogenous substances, the expression of ABCG2 undergoes alterations that result in modifications in its function and activity. Genetic variants in the ABCG2 transporter can potentially impact its expression and function, contributing to the development of many disorders. This review aimed to illustrate the impact of ABCG2 expression and its variants on oral drug bioavailability, MDR in specific cancer cells, explore the relationship between ABCG2 expression and other disorders such as gout, Alzheimer's disease, epilepsy, and erythropoietic protoporphyria, and demonstrate the influence of various synthetic and natural compounds in regulating ABCG2 expression. [Display omitted] •ABCG2 is an important transporter protein in biological systems.•Role of ABCG2 in multidrug resistance and other disoreders•Genetic variants of ABCG2 can affect diseases and oral bioavailability of drugs.•Importance of ABCG2 protein modulators.