SPEG
SPEG, the striated muscle-enriched protein kinase, pairs immunoglobulin-like repeats with two distinct serine/threonine kinase domains and is essential for cardiac development and skeletal muscle maturation. The first kinase domain phosphorylates phospholamban and myosin-binding protein C to modulate calcium handling and contraction, while the second acts on junctophilin-2, maintaining T-tubule structure in cardiomyocytes. SPEG also phosphorylates myotubularin, and its loss causes centronuclear myopathy-like pathology. SPEG knockout mice die with dilated cardiomyopathy, and human SPEG variants are found in cardiomyopathy and myopathy cohorts, positioning this CAMK-group kinase as a regulator of excitation-contraction coupling machinery.
