Glycosylation and hydroxylation are among the most common PTMs in ECM proteins. Importantly, they constitute non-reversible modifications, but reversible PTMs such as phosphorylation and sulfonation also occur. For example, the transmembrane collagen XVII can be phosphorylated and this mechanism regulates shedding of its ectodomain.95 Similarly, phosphorylation of osteopontin inhibits vascular calcification.96 In a study by Lundby et al.97 proteomics was used to identify phosphosites on 14 different rat tissues including hearts. Phosphopeptides were enriched using titanium dioxide. Notably, many previously unrecognized phosphosites were reported in ECM proteins including several collagens and non-collagenous ECM proteins such as laminins, fibronectin, versican, and decorin to name a few. This methodology was effective on fresh animal tissues, but has yet to be applied to the context of cardiac disease. Challenges to its application will include preservation of short-lived PTMs in patient samples and during sample preparation.