An extracellular matrix (ECM) is a network of numerous macromolecules that represents the cellular structural support involved in key biofunctions such as signal transduction and cellular adhesion. In addition, ECM-associated proteins interact with ECM and with other endogenous structures and molecules to control cellular growth, structural modifications, cellular migration, etc. Among the ECM-associated proteins, secreted protein acidic and rich in cysteine (SPARC) is a protein that is known to be expressed when tissues change. Herein, we put a spotlight on selected, metabolic and homeostatic properties beyond the known properties of ECM and SPARC. Importantly, the synchronization of the metabolic and structural implications of SPARC and the ECM would indicate an adaptation of the metabolism to meet the needs of the changes that the tissues undergo. Highlighting such properties would have important applications in diverse fields that include therapeutics, metabolics, and pathogenesis.