Ryanodine receptor 2

Ryanodine receptor 2 (RYR2) is a cytosolic calcium-activated calcium channel that mediates the release of Ca²⁺ from the sarcoplasmic reticulum into the cytosol, playing a key role in triggering cardiac muscle contraction and maintaining cellular calcium homeostasis (UniProt: Q92736). The protein is also required for embryonic heart development, and its aberrant activation can lead to cardiac arrhythmia. RYR2 forms functional heterotetramers with RYR3 to modulate calcium channel activity in cardiac myocytes.

RYR2 is primarily associated with cardiac function and disease. UniProt documents two major disease associations: catecholaminergic polymorphic ventricular tachycardia (CPVT1), an autosomal dominant stress-induced arrhythmogenic disorder, and ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome (VACRDS). Both conditions present with syncope, cardiac arrest, and sudden death risk, typically triggered by physical exertion or emotional stress (UniProt: Q92736).

RYR2 is downregulated in Alzheimer's Disease brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.456 in human post-mortem AD brain analyzed via TMT-labeled quantitative proteomics. This decrease may reflect altered calcium homeostasis in AD pathology, though the functional significance in neuronal contexts requires further investigation.