CLCA1 (chloride channel accessory 1) functions primarily as a regulator of calcium-activated chloride conductance and mucus production in epithelial tissues. The protein facilitates the activity of TMEM16A (Anoctamin-1), a Ca2+-dependent Cl- channel, forming a functional chloride current axis 1. CLCA1 is secreted by goblet cells alongside other mucus components and plays a critical role in mucin regulation, specifically inducing MUC5AC expression in airway epithelium 23. The gene is prominently expressed in respiratory and gastrointestinal tissues where it contributes to innate immune responses and barrier function. Clinically, CLCA1 is significantly relevant in respiratory diseases, particularly asthma, where its expression in nasal epithelium serves as a biomarker for asthma endotypes and reflects lower airway pathology 4. In diabetic kidney disease, CLCA1 upregulation associates with kidney injury through mTORC1 activation and matrix protein accumulation 1. The protein also functions in intestinal innate immunity, with its release affected by bitter taste receptor signaling 5. Additionally, CLCA1 has emerged as a potential biomarker in colorectal cancer through aberrant N-glycosylation patterns 6. Therapeutic targeting of CLCA1 pathways shows promise for treating mucus overproduction in chr1 airway diseases 7.