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Its activity is fine‐tuned by post‐translational modifications—being activated through histidine phosphorylation by NDPK‐B and inhibited by dephosphorylation via PHPT‐1—and the channel is dynamically recruited to the immunological synapse of T cells. Moreover, adenosine acting through A₂A receptors and β₂‐adrenoceptor signaling in mast cells suppress KCNN4 activity, thereby modulating chemotaxis and cytokine release and ultimately influencing adaptive and innate immune responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nKCNN4 also contributes significantly to vascular and proliferative processes. It is up‐regulated in vascular smooth muscle cells and participates in cell proliferation and migration—in models of atherosclerosis, prostate cancer, and diabetic nephropathy, for example—with pharmacological blockade or gene silencing diminishing VSMC activation, oxidative stress, and fibroblast-driven tissue remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer, KCNN4 activity has been linked to enhanced tumor cell migration, invasion, and epithelial–mesenchymal transition across several malignancies—including glioblastoma, colorectal, angiosarcoma, and breast cancers—with elevated channel expression correlating with worsened prognosis. Experimental inhibition of KCNN4 suppresses these processes, highlighting its potential as a therapeutic target for limiting tumor spread and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, KCNN4 functions in excitable tissues such as the heart and brain. Structural and electrophysiological studies in human embryonic stem cell–derived cardiomyocytes and neurons have revealed that KCNN4 contributes to pacemaker activity and regulates neuronal excitability by shaping the diastolic potential, thereby influencing both cardiac rhythm and central nervous system function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn epithelial systems, KCNN4 facilitates Cl⁻ secretion and fluid transport in airways, kidneys, and possibly at the blood–brain barrier. 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