Cells interact with a network of proteins in the microenvironment known as the extracellular matrix (ECM). The functional importance of the ECM goes beyond structural support within the tissue. Components of the ECM interact with cells transmitting signals that regulate adhesion, migration, proliferation, apoptosis, or differentiation. In this presentation, we will focus on the ECM first in adipose tissue and secondly in failing heart tissue. We will discuss findings from a transgenic knockout mouse model for laminin alpha 4, a key component of adipose ECM.