Pathological roles of transient receptor potential channels in chronic obstructive pulmonary disease: special focus on cellular mechanisms

INTRODUCTION: Transient receptor potential (TRP) channels comprise a superfamily of cation-permeable channels broadly expressed in the respiratory tract, playing essential roles in regulating epithelial integrity, mucus secretion, mechanotransduction, and innate immune responses. Increasing evidence suggests that dysregulation of TRP channels contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD). AREAS COVERED: This review summarizes current insights into the cellular mechanisms by which TRP channels contribute to COPD, with particular emphasis on respiratory epithelial dysfunction while also incorporating selected non-epithelial mechanisms relevant to disease pathogenesis. A comprehensive literature search was conducted in PubMed and Web of Science up to January 2026. EXPERT OPINION: Evidence for TRP involvement in COPD is heterogeneous. TRPV4 currently has the strongest mechanistic and translational support, whereas TRPC1 and TRPC6 still require further therapeutic validation. TRPV2 appears to be linked more specifically to macrophage dysfunction and emphysema-related pathology, whereas the roles of TRPV6 and TRPM6 are still incompletely defined. A key barrier to clinical translation is that numerous TRP-targeted strategies have been developed outside COPD or have shown limited efficacy in the clinical settings tested to date, while safety concerns also remain. Future progress will require COPD-specific validation, localized delivery, and biomark...