Fibronectin type III domain-containing protein 5 (FNDC5)

Fibronectin type III domain-containing protein 5 (FNDC5) is a type I transmembrane protein primarily expressed in skeletal muscle and adipose tissue, where its expression is significantly induced by physical exercise and the transcriptional coactivator PGC-1alpha (Boström et al., 2012; UniProt Q8NAU1). FNDC5 undergoes proteolytic cleavage to release a 112-amino acid peptide called Irisin into the bloodstream, which acts as a myokine and adipokine (Boström et al., 2012). Irisin's primary biological role involves the 'browning' of white adipose tissue by upregulating Uncoupling Protein 1 (UCP1), thereby increasing thermogenesis and energy expenditure (Islam et al., 2021). Beyond metabolism, FNDC5/Irisin plays a crucial role in the central nervous system by promoting the expression of Brain-Derived Neurotrophic Factor (BDNF), which supports cognitive function and neuroprotection (Wrann et al., 2013). It also interacts with integrin receptors (alphaV/beta5) in bone and fat tissues to regulate remodeling and metabolic signaling (Kim et al., 2018). Due to its diverse roles, FNDC5 is a high-interest therapeutic target for treating obesity, type 2 diabetes, and neurodegenerative conditions like Alzheimer's disease (Islam et al., 2021).

Other names

IrisinFRCP2Fibronectin type III repeat-containing protein 2PeP

FNDC5 is a precursor protein that is proteolytically cleaved to release the hormone Irisin. Irisin binds to the integrin alphaV/beta5 receptor complex, activating downstream signaling pathways such as p38 MAPK and ERK1/2. This signaling induces the expression of thermogenic genes like UCP1 in white adipose tissue and neurotrophic factors like BDNF in the brain (Boström et al., 2012; Wrann et al., 2013; Kim et al., 2018).