Cellular Models and Functional Assays for Assessing CFTR Function: A Comprehensive Review.

Cystic fibrosis (CF) is a genetic disorder caused by dysfunction of the CFTR chloride ion channel. Progress in molecular understanding and therapy development relies on advanced cellular models and robust assays for evaluating CFTR function. This review traces the evolution of in vitro models, from primary and immortalized cell lines to patient-specific induced pluripotent stem cells (iPSCs) and complex three-dimensional systems. These advanced models, including air-liquid interface (ALI) cultures, organoids, and microfluidic organ-on-a-chip platforms, enable recapitulation of tissue architecture, cellular heterogeneity, and key pathological features such as impaired mucociliary clearance and chronic inflammation. A critical component of CF research is the accurate functional assessment of CFTR activity. We compare established high-resolution techniques (patch-clamp, Ussing chamber) with high-throughput screening assays, including fluorescence quenching of halide-sensitive YFP assay and organoid swelling tests. The article provides a framework for choosing the most appropriate CFTR functional assay tailored to specific research goals.