Recently, Professor Sun Jinpeng’s team at Shandong University and collaborators published a research paper titled “A force-sensitive adhesion GPCR is required for equilibrioception” in Cell Research. This study employed high-throughput screening combined with animal models and electrophysiological recordings to identify LPHN2, a G protein-coupled receptor (GPCR) expressed at the apical membrane of vestibular hair cells, as a critical receptor for balance perception. The research revealed that LPHN2 functionally couples with TMC1 at the vestibular hair cell apical surface to regulate tip link-independent MET processes. Force-induced LPHN2 activation promotes the intracellular calcium signaling and glutamate secretion in hair cells, contributing to equilibrioception. This discovery reshapes the theoretical framework of balance perception mechanisms, positioning GPCRs as core mechanosensory receptors and unveiling a “dual-track” mechanotransduction system in equilibrioception. The findings are expected to provide novel therapeutic targets for balance-related disorders.

Balance sensation, which is a core sense that enables humans to perceive three-dimensional space, relies on the coordinated functions of the vestibular system, visual system, and proprioceptive system. The vestibular system functions as the primary regulator of equilibrioception and detects spatial orientation and motion of the head and body. Vestibular dysfunction leads to symptoms such as vertigo and imbalance, severely impacting patients’ quality of life. Vestibular hair cells residing at the epithelium of vestibular organs convert extracellular mechanical signals into electrical signals through mechanoelectrical transduction (MET), a core process in balance perception. In recent years, multiple components of the MET channel, such as TMC1/2, TMIE, and LHFPL5, have been identified, but their precise regulatory mechanisms remain incompletely understood.