G protein-coupled receptors (GPCRs) play critical roles in transmitting a variety of extracellular signals into the cells and regulate diverse physiological functions. Naturally occurring mutations that result in dysfunctions of GPCRs have been known as the causes of numerous diseases. Significant progresses have been made in elucidating the pathophysiology of diseases caused by mutations. The multiple intracellular signaling pathways, such as G protein-dependent and β-arrestin-dependent signaling, in conjunction with recent advances on biased agonism, have broadened the view on the molecular mechanism of disease pathogenesis. This review aims to briefly discuss biased agonism of GPCRs (biased ligands and biased receptors), summarize the naturally occurring GPCR mutations that cause biased signaling, and propose the potential pathophysiological relevance of biased mutant GPCRs associated with various endocrine diseases.

G蛋白偶联受体（GPCR）在将多种细胞外信号传递至细胞内并调节多种生理功能方面发挥着关键作用。导致 GPCR 功能障碍的自然发生突变已被认为是许多疾病的原因。在阐明突变引起的疾病的病理生理学方面已经取得了重大进展。多种细胞内信号通路，例如G蛋白依赖性和β-抑制蛋白依赖性信号传导，结合偏向激动的最新进展，拓宽了对疾病发病机制分子机制的认识。本综述旨在简要讨论 GPCR（偏向配体和偏向受体）的偏向激动作用，总结导致偏向信号传导的自然发生的 GPCR 突变，并提出偏向突变 GPCR 与各种内分泌疾病相关的潜在病理生理学相关性。