Representation of the role of MARCKS in VSMCs and VECs, showing that unstimulated MARCKS is expressed at the plasma membrane where it forms electrostatic interactions with PIP₂. Cell stimulation by G-protein-coupled and tyrosine kinase receptors induces to phosphorylation MARCKS by various mechanisms including protein kinase C (PKC), Ca²⁺-calmodulin (CaM), and H₂O₂ production, leading to the translocation of MARCKS from the plasma membrane into the cytoplasm and release of PIP₂ into the local environment where it interacts with transmembrane proteins. Both phosphorylation and translocation of MARCKS and PIP₂–protein interactions were associated with changes in cell function such as proliferation and migration, endothelial barrier permeability, and smooth muscle contractility.

The IRE1α signaling pathway plays a critical role in the pathology of various vascular diseases.