PLEKHA7 was identified by mass spectrometry in lysates of human intestinal carcinoma (Caco-2) cells in a GST-pull down using N-terminal GST-fusion p120 catenin as bait.

[5] It was also independently discovered in Sandra Citi’s group as a protein interacting with globular head domain of the Paracingulin in a yeast two-hybrid screen.

[6] The first identified function of PLEKHA7 was is to contribute to integrity and stability of the zonula adherens junctions by linking the E-cadherin/p120 complex to the minus ends of microtubules (MTs) through Nezha (CAMSAP3).

[7] PLEKHA7 knockdown studies in Madin-Darby canine kidney (MDCK) cells indicated its requirement for the AJ localization of paracingulin.

[9] Furthermore, the PLEKHA7 homolog in zebrafish, Hadp1, is required for proper heart function and morphogenesis in embryo, regulating the intracellular Ca2+ dynamics through the phosphatidylinositol 4-kinase (PIK4) pathway.

[11][12][13] In 2015 it was also discovered that PLEKHA7 has a role in controlling susceptibility to Staphylococcus aureus alpha-toxin [14] Cells lacking PLEKHA7 are injured by the toxin, but recover after intoxication.

[15] In the absence of either PLEKHA7 or PDZD11, the amount of nectin-3 and nectin-4 detected at junctions is decreased, as well as total nectin levels, through proteasome-mediated degradation.