Regulation of Ca2+ Signals in Human Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 2342

Special Issue Editor


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Guest Editor
Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA 17033, USA
Interests: Ca2+ signaling; STIM/Orai pathway
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Special Issue Information

Dear Colleagues,

Calcium (Ca2+) signaling plays a pivotal role in a wide range of physiological processes, including gene expression, cell proliferation, metabolism, and apoptosis. The dysregulation of Ca2+ homeostasis is increasingly recognized as a contributing factor in the pathogenesis of numerous human diseases, such as cancer, neurodegenerative disorders, cardiovascular disease, and immune dysfunction. This Special Issue of Cells will highlight recent advances in our understanding of how Ca2+ signaling is regulated under physiological and pathological conditions. We welcome original research articles and reviews that explore molecular mechanisms, disease models, therapeutic targets, and novel imaging or analytical tools related to Ca2+ signaling in human health and disease.

Dr. Yandong Zhou
Guest Editor

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Keywords

  • calcium signaling
  • cellular homeostasis
  • disease mechanisms
  • calcium channels
  • therapeutic targets

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Published Papers (1 paper)

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Review

14 pages, 850 KB  
Review
The Interplay Between Ca2+ Homeostasis, Endoplasmic Reticulum Stress, and the Unfolded Protein Response in Human Diseases
by Elia Ranzato and Simona Martinotti
Cells 2026, 15(4), 352; https://doi.org/10.3390/cells15040352 - 15 Feb 2026
Cited by 3 | Viewed by 1986
Abstract
The maintenance of endoplasmic reticulum (ER) Ca2+ homeostasis is intrinsically linked to the fidelity of protein folding, forming a functional tether that, when disrupted, triggers the Unfolded Protein Response (UPR). This bidirectional axis serves as a critical rheostat for cellular viability, yet [...] Read more.
The maintenance of endoplasmic reticulum (ER) Ca2+ homeostasis is intrinsically linked to the fidelity of protein folding, forming a functional tether that, when disrupted, triggers the Unfolded Protein Response (UPR). This bidirectional axis serves as a critical rheostat for cellular viability, yet its chronic dysregulation underpins the molecular etiology of numerous pathologies, including neurodegeneration, heart failure, and malignant transformation. This review provides a comprehensive interrogation of the Ca2+-ER Stress–UPR network, delineating how primary stress sensors—PERK, IRE1alpha, and ATF6—engage in complex feedback loops that either reinstate equilibrium or commit the cell to apoptosis. We specifically examine the PERK-CHOP-SERCA2b inhibitory circuit as a central driver of persistent Ca2+ depletion and discuss the role of Mitochondria-Associated Membranes (MAMs) in governing lethal Ca2+ transfer. Notably, we move beyond the classical paradigm of CHOP as a terminal apoptotic executioner, incorporating emerging evidence of its context-dependent adaptive functions. By synthesizing mechanistic insights across diverse disease models, this work highlights the transition from adaptive to maladaptive UPR as a universal pathological checkpoint. Ultimately, we evaluate the therapeutic potential of ‘axis-targeted’ interventions, such as SERCA activators and selective UPR modulators, aimed at resolving the underlying Ca2+ signaling defects in ER stress-related disorders. Full article
(This article belongs to the Special Issue Regulation of Ca2+ Signals in Human Disease)
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