FOXI1 is a forkhead box transcription factor that functions as a critical regulator of specialized epithelial cell development across multiple organ systems. In the inner ear, FOXI1 drives expression of SLC26A4/PDS, JAG1, and COCH, which are essential for endolymphatic system development and normal hearing and balance function 1. In the kidney, FOXI1 directs differentiation of intercalated cells in distal renal tubules through activation of SLC4A1/AE1, SLC4A9/AE4, and ATP6V1B1, enabling acid-base homeostasis and urinary acidification 23. FOXI1 has recently been identified as the master transcription factor for pulmonary ionocytes in the conducting airway epithelium 45. These rare FOXI1+ ionocytes are the primary source of cystic fibrosis transmembrane conductance regulator (CFTR) expression and mediate critical ion transport functions regulating airway surface liquid pH, volume, and mucus properties 6. FOXI1 knockout in ionocytes abolishes CFTR expression and causes cystic fibrosis-like airway pathology. Pathogenic FOXI1 variants are associated with distal renal tubular acidosis (dRTA) and sensorineural hearing loss with inner ear malformations (DFNB4) 21. Additionally, FOXI1 functions as a master transcription factor in chr5 renal cell carcinoma histogenesis 7.