biostudies-literatureKhananshvili DIsraeli Science FoundationIsrael Science Foundation61https://www.ebi.ac.uk/biostudies/studies/S-EPMC9820601biostudies-literatureUnknown24(1)The plasma-membrane homeostasis Na⁺/Ca²⁺ exchangers (NCXs) mediate Ca²⁺ extrusion/entry to dynamically shape Ca²⁺ signaling/in biological systems ranging from bacteria to humans. The NCX gene orthologs, isoforms, and their splice variants are expressed in a tissue-specific manner and exhibit nearly 10⁴-fold differences in the transport rates and regulatory specificities to match the cell-specific requirements. Selective pharmacological targeting of NCX variants could benefit many clinical applications, although this intervention remains challenging, mainly because a full-size structure of eukaryotic NCX is unavailable. The crystal structure of the archaeal NCX_Mj, in conjunction with biophysical, computational, and functional analyses,International journal of molecular sciencesStructure-Based Function and Regulation of NCX Variants: Updates and Challenges.PMC98206011351/18852/14Khananshvili DfalseStructure-Based Function and Regulation of NCX Variants: Updates and Challenges.The plasma-membrane homeostasis Na⁺/Ca²⁺ exchangers (NCXs) mediate Ca²⁺ extrusion/entry to dynamically shape Ca²⁺ signaling/in biological systems ranging from bacteria to humans. The NCX gene orthologs, isoforms, and their splice variants are expressed in a tissue-specific manner and exhibit nearly 10⁴-fold differences in the transport rates and regulatory specificities to match the cell-specific requirements. Selective pharmacological targeting of NCX variants could benefit many clinical applications, although this intervention remains challenging, mainly because a full-size structure of eukaryotic NCX is unavailable. The crystal structure of the archaeal NCX_Mj, in conjunction with biophysical, computational, and functional analyses,2022-01-01T00:00:00Z2022 Dec2025-06-01T02:35:27.476Z2024-11-15T07:49:40.776ZS-EPMC98206013661352310.3390/ijms24010061