FOXI2 (forkhead box I2) is a transcription factor that functions as a DNA-binding regulatory protein with roles in development and disease. During embryonic development, FOXI2 is expressed in the chordamesoderm during early somitogenesis and later in the retina and pharyngeal arches 1. The protein localizes to the basal cell layer of skin and co-localizes with P63, suggesting involvement in ectodermal development 2. FOXI2 appears to function as part of an evolutionary-conserved ionocyte signature, being expressed alongside FOXI1 and other markers in specialized salivary gland cells that regulate ionic modification of saliva 3. In disease contexts, FOXI2 promoter hypermethylation serves as a biomarker in multiple cancers. It is methylated in >50% of colorectal cancers and shows very low methylation in peripheral blood, making it suitable for blood-based diagnostic markers 4. FOXI2 methylation is also associated with oral cancer development, where patients with high FOXI2 promoter methylation have worse cancer-free survival 5. Additionally, FOXI2 methylation-based models show prognostic value in kidney renal clear cell carcinoma 6 and esophageal adenocarcinoma 7. A de novo FOXI2 deletion has been associated with ectodermal dysplasia features 2.