Slc8b1, encoding the mitochondrial Na+/Ca2+ exchanger (NCLX), plays a crucial role in calcium homeostasis, particularly in extruding Ca2+ out of mitochondria. It is associated with pathways like store-operated calcium entry (SOCE), which is vital for immune function, and impacts mitochondrial function, cell metabolism, and cell death signalling [1,2,3]. Genetic models such as knockout mice are valuable for studying its function.

In B-cell specific Slc8b1 knockout mice, loss of Slc8b1 led to reduced SOCE, increased mitochondrial oxidant production, decreased bioenergetics, and altered mitochondrial ultrastructure, along with reduced germinal center B cell responses following antigen and pathogen-driven immune responses [1]. In adult mouse hearts, tamoxifen-induced deletion of Slc8b1 caused sudden death, severe myocardial dysfunction, and heart failure due to mCa2+ overload, superoxide generation, and necrotic cell death [2]. Smooth muscle-specific NCLX KO mice were protected against airway remodeling, fibrosis, and hyperresponsiveness in an asthma model, as NCLX is necessary for airway smooth muscle cell proliferation and migration [4].

In summary, Slc8b1 is essential for maintaining calcium homeostasis and mitochondrial function. Studies using Slc8b1 KO/CKO mouse models have revealed its significant contributions to immune responses, cardiac function, and asthma-related airway pathologies, highlighting its potential as a therapeutic target in these disease areas.