A comprehensive new review highlights the expanding importance of Lgr6, a member of the G protein-coupled receptor family, as a critical regulator of tissue homeostasis, injury repair, and disease development across multiple organ systems. Widely expressed in tissues such as the skin, kidney, lung, and intestine, Lgr6 plays a fundamental role in coordinating cellular behavior and maintaining biological balance.
The article outlines how Lgr6 functions as a key marker of stem and progenitor cells, supporting processes including cell growth, differentiation, and regeneration. Its presence in diverse tissues underscores its importance in normal development, particularly in organ formation and repair following injury. In the skin, for example, Lgr6-positive cells contribute to wound healing and hair follicle regeneration, while in the kidney and lung, they are involved in maintaining structural integrity and restoring damaged tissue.
At the molecular level, Lgr6 exerts its influence through major signaling pathways, notably Wnt/β-catenin and PI3K/AKT, which govern essential cellular functions. By modulating these pathways, Lgr6 helps control cell proliferation, apoptosis, and migration, processes that are vital not only for normal physiology but also for disease progression.
The review also highlights the complex role of Lgr6 in a wide spectrum of diseases. Abnormal expression of this receptor has been observed in conditions affecting the respiratory, digestive, cardiovascular, and reproductive systems, as well as in multiple forms of cancer. In these contexts, Lgr6 can influence tumor initiation, growth, and metastasis, as well as broader pathological changes such as inflammation and fibrosis.
In addition to its biological functions, Lgr6 is closely linked to clinical outcomes. Variations in its expression are associated with disease severity, patient prognosis, and treatment response, particularly in cancers where elevated levels often correlate with more advanced disease and reduced survival.
Importantly, Lgr6 is also connected to tissue regeneration strategies, offering potential applications in areas such as wound repair, bone healing, and degenerative disease management. Its dual role in both promoting regeneration and contributing to disease highlights the need for precise, context-dependent approaches when considering its clinical relevance.
Overall, Lgr6 is positioned as a highly versatile and influential biological regulator. Its widespread involvement in fundamental cellular processes and disease mechanisms underscores its growing significance as both a diagnostic biomarker and a potential therapeutic target, opening new avenues for innovation across biomedical science and medicine.
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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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Reference
Han Li, Xiaoqi Guan, Yu Wang, Haidong Guo, Lgr6+ cells in the biological system during homeostasis and injury, Genes & Diseases, Volume 13, Issue 4, 2026, 101863, https://doi.org/10.1016/j.gendis.2025.101863

Funding
National Natural Science Foundation of China 82174120
Traditional Chinese Medicine Research Project of Shanghai Municipal Health Commission of China 2024PT005
Program of Shanghai Academic Research Leader (China) 22XD1423400