stargazin

Stargazin is a protein that plays a critical role in the function of voltage-gated calcium channels (VGCCs), specifically those of the Cav1.2 subtype, which are essential for calcium influx in excitable cells such as neurons and cardiomyocytes. First identified in 2001 through studies on the *stargazer* mouse mutant, which exhibits severe neurological disorders including epilepsy and ataxia, stargazin belongs to the transmembrane AMPA receptor regulatory protein (TARP) family. Its name derives from the *stargazer* phenotype, where affected mice exhibit a characteristic head-tilting behavior resembling "stargazing."

Structurally, stargazin is a single-pass transmembrane protein with an extracellular N-terminus and a cytoplasmic C-terminus. It modulates the trafficking, surface expression, and biophysical properties of Cav1.2 channels, enhancing their current density and accelerating activation kinetics. This modulation is particularly important in the brain, where Cav1.2 channels regulate neurotransmitter release, synaptic plasticity, and neuronal excitability. Mutations in the gene encoding stargazin (*Cacna2d2*) have been linked to human neurological disorders, including epilepsy, autism spectrum disorders, and intellectual disability, highlighting its significance in human health.

Beyond its role in calcium channels, stargazin also interacts with other proteins, including scaffolding molecules like PDZ-domain-containing proteins, which further influence its localization and function. Research on stargazin continues to explore its potential as a therapeutic target for neurological diseases, as well as its broader implications in cellular signaling and physiology. The protein’s dual role in both neuronal and cardiac systems underscores its broad physiological relevance.