TRPM2

Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a is_associated_with::protein that in humans is encoded by the TRPM2 is_associated_with::gene.

Function
The TRPM2 gene is highly expressed in the brain and was implicated by both genetic linkage studies in families and then by case control or trio allelic association studies in the genetic aetiology of is_associated_with::bipolar affective disorder (Manic Depression).

The physiological role of TRPM2 is not well understood. It was shown to be involved in is_associated_with::insulin secretion. In the is_associated_with::immune cells it mediates parts of the responses to is_associated_with::TNF-alpha. A role has been suggested for TRPM2 in activation of is_associated_with::NLRP3 inflammasome, the dysregulation of which is strongly associated with a number of auto inflammatory and metabolic diseases, such as gout, obesity and diabetes. In the brain it is involved in the toxicity of is_associated_with::amyloid beta, a protein associated with is_associated_with::Alzheimer's disease.

Structure
The protein encoded by this gene is a non-selective calcium-permeable cation channel and is part of the is_associated_with::Transient Receptor Potential ion channel super family. The closest relative is the cold and is_associated_with::menthol activated is_associated_with::TRPM8 ion channel. While TRPM2 is not cold sensitive it is activated by heat. The TRPM2 ion channel is activated by free intracellular is_associated_with::ADP-ribose in synergy with free intracellular is_associated_with::calcium. ADP-Ribose is produced to by the enzyme PARP in response to oxidative stress and confers susceptibility to is_associated_with::cell death. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.