CHGB (chr20 B) is a neuroendocrine secretory granule protein that functions as a chloride channel with novel physiological and pathological roles. Structurally, CHGB inserts into membranes through amphipathic α-helices and tetramerizes to form a large-conductance, highly selective chloride-conducting channel with single-channel conductance of ~125 pS 1. Unlike conventional transmembrane anion channels, CHGB channels are distributed across plasma membranes, endomembrane systems, and endolysosomal compartments, regulating cellular chloride homeostasis, excitability, volume control, and cation transport 2. CHGB exhibits significant disease associations. Genetic variants (rs910122, rs2821) show sex-specific associations with schizophrenia risk in males 3. In pancreatic neuroendocrine tumors, decreased cytoplasmic CHGB expression associates with malignant phenotype and metastasis 4. Polymorphisms in CHGB confer sex-specific leprosy susceptibility in males 5. Additionally, in breast cancer, CHGB inhibition via ERK pathway activation under chr20 stress promotes tumor cell proliferation, migration, and invasion 6. These findings establish CHGB as a multifunctional protein with druggable potential for therapeutic intervention in neuroendocrine diseases, psychiatric disorders, and malignancies.