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The repercussions of cilia dysmotility and gene variants on the multiciliated cell remain poorly understood. We used single-cell RNA-Seq, proteomics, and advanced microscopy to compare primary culture epithelial cells from patients with PCD, their heterozygous mothers, and healthy individuals, and we induced pluripotent stem cells (iPScs) generated from a patient with PCD. Transcriptomic analysis revealed unique signatures in PCD airway cells compared with their mothers\u2019 cells and the cells of healthy individuals. Gene expression in heterozygous mothers\u2019 cells diverged from both control and PCD cells, marked by increased inflammatory and cellular stress signatures. Primary and iPS-derived PCD multiciliated cells had increased expression of glutathione-S-transferases\n                    <jats:italic>GSTA2<\/jats:italic>\n                    and\n                    <jats:italic>GSTA1<\/jats:italic>\n                    , as well as NRF2 target genes, accompanied by elevated levels of reactive oxygen species (ROS). Immunogold labeling in human cilia and proteomic analysis of the ciliated organism\n                    <jats:italic>Chlamydomonas reinhardtii<\/jats:italic>\n                    demonstrated that GSTA2 localizes to motile cilia. Loss of human GSTA2 and\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>reinhardtii<\/jats:italic>\n                    GSTA resulted in slowed cilia motility, pointing to local cilia regulatory roles. Our findings identify cellular responses unique to PCD variants and independent of environmental stress and uncover a dedicated ciliary GSTA2 pathway essential for normal motility that may be a therapeutic target.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.180198","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T12:08:30Z","timestamp":1721736510000},"source":"Crossref","is-referenced-by-count":15,"title":["Transcriptional analysis of primary ciliary dyskinesia airway cells reveals a dedicated cilia glutathione pathway"],"prefix":"10.1172","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4556-8455","authenticated-orcid":true,"given":"Jeffrey R.","family":"Koenitzer","sequence":"first","affiliation":[{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepesh Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington 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