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Perturbations in cardiac Ca2+ handling through altered kinase activity has been implicated in altered cardiac contractility and arrhythmogenesis. Thus, a better understanding of cardiac Ca2+ handling regulation is vital for a better understanding of various human disease processes. \u2018Striated muscle preferentially expressed protein kinase\u2019 (SPEG) is a member of the myosin light chain kinase family that is key for normal cardiac function. Work within the last 5 years has revealed that SPEG has a crucial role in maintaining normal cardiac Ca2+ handling through maintenance of transverse tubule formation and phosphorylation of junctional membrane complex proteins. Additionally, SPEG has been causally impacted in human genetic diseases such as centronuclear myopathy and dilated cardiomyopathy as well as in common acquired cardiovascular disease such as heart failure and atrial fibrillation. Given the rapidly emerging role of SPEG as a key cardiac Ca2+ regulator, we here present this review in order to summarize recent findings regarding the mechanisms of SPEG regulation of cardiac excitation\u2013contraction coupling in both physiology and human disease. A better understanding of the roles of SPEG will be important for a more complete comprehension of cardiac Ca2+ regulation in physiology and disease.<\/jats:p>","DOI":"10.1093\/cvr\/cvaa290","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T15:11:03Z","timestamp":1601651463000},"page":"2175-2185","source":"Crossref","is-referenced-by-count":35,"title":["SPEG: a key regulator of cardiac calcium homeostasis"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-9503","authenticated-orcid":false,"given":"Hannah","family":"Campbell","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, Baylor College of Medicine , One Baylor Plaza, BCM335, Houston, TX 77030,","place":["USA"]},{"name":"Department of Molecular Physiology & Biophysics, Baylor College of Medicine , Houston, TX 77030,","place":["USA"]},{"name":"Medical Scientist Training Program, Baylor College of Medicine , Houston, TX 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