Calcium homeostasis modulator (CALHM) family, also known as FAM26 proteins, is a group of voltage-gated ion channel proteins (CALHM1-6). These proteins are widely expressed in the brain and taste buds throughout vertebrates and in sensory neurons and body wall muscles in C. elegans. They have an essential roles in the regulation of calcium homeostasis in various cells, participating in a variety of biological processes, such as neuronal excitability, neurotransmission of tastes, and muscle cell function.
CALHM1 have been shown to mediate of neuronal intracellular calcium homeostasis and signaling, and calcium-dependent neuronal excitability and memory in mouse models. In human, CALHM1 regulates the Ca2+ dependent MEK, ERK, RSK and MSK signalling cascade in neurons. It may be associated with the pathogenesis of Alzheimer's disease (AD). CALHM2/CALHM3 is a paralogue of CALHM1 that participates in the controlling neuronal excitability. CALHM4/CALHM5/CALHM6 is probably a pore-forming subunit of a voltage-gated ion channel. The following table further illustrates some members of the family.
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