GroganPflugersArchiv'18.pdf

Obscurins, expressed from the single OBSCN gene, are a family of giant, modular, cytoskeletal proteins that play key structuraland regulatory roles in striated muscles. They were first implicated in the development of heart disease in 2007 when twomissense mutations were found in a patient diagnosed with hypertrophic cardiomyopathy (HCM). Since then, the discovery ofover a dozen missense, frameshift, and splicing mutations that are linked to various forms of cardiomyopathy, including HCM,dilated cardiomyopathy (DCM), and left ventricular non-compaction (LVNC), has highlighted OBSCN as a potential diseasecausinggene. At this time, the functional consequences of the identified mutations remain largely elusive, and much work has yetto be done to characterize the disease mechanisms of pathological OBSCN variants. Herein, we describe the OBSCN mutationsknown to date, discuss their potential impact on disease development, and provide future directions in order to better understandthe involvement of obscurins in heart disease