One α and one β subunit associate non-covalently to form 24 unique integrins found in mammals.

The β6 subunit and ITGB6 sequence was discovered by Professor Dean Sheppard and colleagues at the University of California, San Francisco in the early 1990s in guinea pig cells.

[10] In the past decade, significant research has been performed toward identifying the location of regions within the ITGB6 gene which both promote and suppress ITGB6 expression.

Of note, binding regions for transcription factors STAT3 and C/EBPα were found, and basic normal cell expression of ITGB6 is thought to be regulated primarily by these proteins.

The mice also developed temporary baldness, possibly due to the role αvβ6 plays in hair follicle regeneration.

[21] Matrix metallopeptidase 12 (MMP12) is an enzyme strongly associated with the development of emphysema, and was expressed 200-fold higher compared to the normal mice in alveolar macrophages.

Incomplete adhesion of the gums to the teeth can cause ‘pockets’ to form which are prone to infection, resulting in chronic periodontal disease.

[25] In most resting normal cells, little ITGB6 is produced, however the highest levels are found in the stomach, gall bladder and lung.

[30] TGF-β1 regulates multiple processes including cell proliferation,[31][32] differentiation,[32] angiogenesis,[33] epithelial-mesenchymal-transition (EMT)[34] and immune suppression.

[36] Chronic activation of fibroblasts can result in diseases such as pulmonary fibrosis,[37] where the hardening and thickening of the lung tissue makes it difficult for patients to breathe.

[43] In cancer, this promotes invasion of the local healthy tissue and ultimately spread to other parts of the body.

The first reported case was in 2013 following whole genome sequencing of a 7-year-old girl with amelogenesis imperfecta,[46] a disease affecting the development of teeth.

While multiple patients with amelogenesis imperfecta have since been found to have ITGB6 mutations,[47][48] there were no other clinical symptoms reported in the majority of these cases.

In 2016 a family in Pakistan were found to have dysfunctional ITGB6 resulting in alopecia, intellectual disabilities and symptoms consistent with amelogenesis imperfecta.

Particularly its overexpression by many types of carcinomas (synonymous to cancers of epithelial origin) has prompted research on radiotracers binding to αvβ6.