{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCNIP2 encodes the multifunctional potassium channel‐interacting protein 2 (KChIP2), an EF‐hand Ca²⁺‐binding accessory subunit that plays a central role in modulating the properties of Kv4 channel complexes. In cardiac myocytes, KChIP2 associates with pore‐forming Kv4 subunits to enhance current density, slow inactivation, and accelerate recovery from inactivation, thereby contributing to the rapid transient outward K⁺ current (Iₜₒ) that critically shapes action potential repolarization and underlies transmural electrophysiological gradients."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Moreover, studies on the stoichiometry and trafficking of Kv4 channel complexes have revealed that KChIP2 not only promotes forward trafficking and stabilizes cell‐surface expression of Kv4 channels but is also itself stabilized by complex formation, leading to robust and finely tuned repolarizing currents."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Beyond its classical role with Kv4 channels, KChIP2 has been shown to modulate other cardiac channels: it can attenuate surface expression of Kv1.5 channels, thus reducing currents that also contribute to the repolarization process"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and it directly interacts with the N terminus of the L‐type Ca²⁺ channel CaV1.2 to augment I(Ca,L), indicating a broader influence on cardiac excitability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, KChIP2 is expressed in neuronal tissues where its differential regional distribution suggests a role in regulating neuronal A‐type currents and excitability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, non‐canonical functions for KChIP2 have emerged in the immune system, where it acts as a Ca²⁺‐dependent transcriptional repressor modulating cytokine gene expression and T‐cell responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these findings demonstrate that KChIP2 functions as a multimodal regulator of ion channel gating, trafficking, and cellular excitability across diverse tissues, with critical implications for both normal physiology and disease‐related electrical remodeling.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Isabelle Deschênes, Gordon F Tomaselli "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of Kv4.3 current by accessory subunits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0014-5793(02)03296-9"}], "href": "https://doi.org/10.1016/s0014-5793(02"}, {"type": "t", "text": "03296-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12297301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12297301"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Isabelle Deschênes, Deborah DiSilvestre, George J Juang, et al. 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