Rev. Biol. Biomed. Sci. 2021 4 (1) 43-57 DOI: 10.31178/rbbs.2021.4.1.3 Cystic fibrosis: a comprehensive review Corina Anghel (Delia), Andreea-Mariana Negrescu, Anisoara Cimpean  1 Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independenței, 050095 Bucharest, Romania; 2 Research Institute of the University of Bucharest, Bucharest, Romania  Correspondence to: Anisoara Cimpean, Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania E-mail: anisoara.cimpean@bio.unibuc.ro Received: 10 March 2022 / Revised: 5 May 2022 / Accepted: 24 May 2022 / Available online: 8 July 2022 Abstract With almost 100 000 people affected worldwide, cystic fibrosis (CF) represents one of the most fatal inherited conditions found in Caucasian individuals, being clinically characterized by a progressive pulmonary dysfunction, pancreatic insufficiency, and male infertility. Alterations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein has been found to be the sole responsible for the disease, with over 2000 defects being identified since 1989. Here we present, at a basic descriptive level, the current understanding of the clinical and genetic traits of CF gene modifications, the challenges associated with the early diagnosis and management strategies but also new emerging therapies that can improve the individual’s life expectancy by enabling patient-specific treatment. Keywords: cystic fibrosis, CFTR mutations, gene therapy, neonatal screening Introduction Cystic fibrosis (CF) is a complex, progressive, monogenic condition, with varying incidence rates that reach as high as 1 affected individual in 2000 to 3000 live births. Despite its long history, the disease was firstly described in 1938 as a clinical syndrome, but it was not until 1989 when gene cloning made possible the discovery of a link between the aberrant CFTR gene expression and the diverse clinical manifestations of the condition (Coakley and Boucher, 2007). However, despite the fact that only a low number of individuals display the long-established clinical manifestations of CF, the rate of carriers for this genetic mutation is remarkably prominent in the population worldwide (Cutting, 2015) and recent research indicated that even carriers for this mutation that exhibit no clinical symptoms could present a risk for various subclinical physiological affections which can be further aggravated by stress or other environmental stimuli (Wang et al., 2000; Cohn et al., 2005). Moreover, even though one of the most common causes of mortality associated with CF is represented by recurrent respiratory infections that lead to early obstructive lung disease and respiratory failure, other organs such as the pancreas, liver, intestine, bones, sinuses, and the male reproductive tract are prone to be affected (Rey et al., 2019), making CF a multisystem illness that can alter any organ with an epithelial origin (Coakley and Boucher, 2007). However, regardless of the massive advances made in the understanding of the genetic and molecular disease mechanisms and clinical progress in diagnosis, unfortunately CF still remains an incurable affection, that when kept under control through an organised lifestyle, individuals can often reach adulthood with the average prognosticated age of survival of 43 for females and 48 for males (Keogh et al., 2018). However, the demanding and often tiresome routine that patients must maintain throughout their life in order to keep their infliction under control can often leave undesirable effects on both their physical, as well as their mental wellbeing (Jaques et al., 2020). With this in mind, the ongoing research focused on therapy improvement that could be directly connected with several important changes in patient care such as nutritional supplementation, airway clearance, long-term antimicrobial treatment (Shteinberg et al., 2021) and very recently the development of small molecule agents named CFTR (Cystic fibrosis transmembrane conductance regulator) modulators that can potentiate the function of the affected protein or restore the low levels of protein found on the surface of the cells (Patel et al., 2020). In this paper we will review the genetic and cellular mechanisms of CF, its pathophysiology and diagnosis methods, followed by management of disease and future approaches for treatment and a potential cure for this condition. Reviews in Biological and Biomedical Sciences