TTYH3 encodes a calcium-activated chloride channel protein that functions as both an ion channel and signaling molecule. As an ion channel, TTYH3 operates as a large-conductance calcium-activated chloride channel and volume-regulated anion channel, facilitating chloride efflux and cellular volume regulation 1. Beyond its channel activity, TTYH3 serves critical roles in cancer progression through channel-independent mechanisms. In hepatocellular carcinoma, TTYH3 interacts with MK5 kinase to activate GSK3β/β-catenin signaling pathways, promoting tumor growth and metastasis 1. The protein also functions in epithelial-mesenchymal transition, facilitating cancer cell migration and invasion across multiple cancer types including colorectal 2, lung 3, and bladder cancers 4. In colorectal cancer, TTYH3 promotes metastasis independently of its ion channel activity through competing endogenous RNA mechanisms with HDAC7 2. Clinically, elevated TTYH3 expression correlates with poor prognosis in multiple cancers including ovarian 5, gastric 6, and lung cancers 7, where it associates with immune infiltration patterns and reduced immunotherapy response. Additionally, TTYH3 can participate in oncogenic fusion proteins, such as TTYH3-BRAF fusions in glioblastoma, where it provides membrane localization that activates BRAF signaling 8.