TTYH2

Tweety Homolog 2 (TTYH2) is a integral membrane protein belonging to the Tweety family, functioning as a calcium-activated chloride channel (CaCC); it has no widely recognized alternative aliases. Localized primarily to the plasma membrane, TTYH2 mediates chloride ion (Cl⁻) transport, with its channel activity triggered by increased intracellular calcium levels. This transport role supports critical cellular processes, including maintaining cell volume homeostasis, regulating epithelial fluid secretion, and modulating neuronal excitability by fine-tuning Cl⁻ flux.
TTYH2’s function is closely tied to calcium signaling pathways, such as those involving inositol 1,4,5-trisphosphate (IP₃) receptors and store-operated calcium entry (SOCE). Dysregulated TTYH2 expression or activity is linked to neurological disorders like epilepsy—where abnormal Cl⁻ conductance disrupts neuronal firing—and certain cancers, including colorectal cancer, associated with impaired cell volume control. Currently, drug development targeting TTYH2 remains in early preclinical phases, focusing on small-molecule modulators to correct ion flux imbalances in pathological states.