{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC9A1, which encodes the Na⁺/H⁺ exchanger NHE1, is a critical plasma membrane protein that maintains intracellular pH and cell volume by extruding protons in exchange for sodium ions. Numerous studies have highlighted that NHE1 activity is intricately regulated by posttranslational modifications and protein–protein interactions. For instance, binding of regulatory factors such as the calcineurin B homologous proteins potentiates NHE1 function, while site‐specific phosphorylation—particularly at residues like Ser770/771—modulates its activity and interactions with downstream effectors to protect cells from apoptotic stresses and serum deprivation (‑."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn pathological settings, NHE1 has been implicated as a key driver of Na⁺ and H⁺ dysregulation that underlies disease progression. In the heart, overactivation of NHE1 contributes to intracellular Na⁺ and Ca²⁺ overload, triggering signaling cascades that promote cardiac hypertrophy and heart failure. In cancer cells, heightened NHE1 activity leads to extracellular acidification at specialized plasma membrane domains—helping to form a proton gradient that activates proteases at invadopodia and facilitates extracellular matrix degradation, enhanced migration, and invasion. Moreover, NHE1 collaborates with membrane receptors and cytoskeletal adaptors, establishing regulated pH microdomains essential for directional migration and metastatic potential, while its dysregulation has been linked to altered ion transport and oncogenic progression (‑."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNHE1 also serves as a scaffold that links cytoskeletal regulatory proteins to membrane microdomains, thereby influencing the formation and stabilization of specialized structures such as leading‐edge invadopodia. Structural studies and computational modeling of its transmembrane segments have provided insights into its conformational dynamics and inhibitor binding sites, which are crucial for its transport mechanism and regulation. 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