Cystic Fibrosis: Modern Diagnostic and Therapeutic Advances from Molecular Pathogenesis to Multidisciplinary Management

Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is increasingly understood through a genomics-informed framework linking variant architecture to phenotype, diagnosis, and therapeutic eligibility. This review summarizes current evidence on CFTR structure, variant interpretation, genotype-phenotype heterogeneity, diagnostic workflows, and modern management. We highlight how full-gene sequencing, curated disease-liability databases, functional testing, and organoid-informed theratyping refine diagnosis and treatment selection; how disrupted chloride and bicarbonate transport drives muco-obstructive airway disease and multisystem complications; and why modulator therapy must still be integrated with respiratory, nutritional, endocrine, hepatobiliary, reproductive, and psychosocial care. We also outline unresolved challenges in rare variants, residual organ damage, ancestry-related diagnostic gaps, and mutation-agnostic therapeutic development.