XIRP1 is a muscle-specific actin-binding protein that protects actin filaments from depolymerization and functions as a scaffolding protein at cardiac intercalated discs and skeletal muscle attachment sites. It interacts with multiple cardiac proteins including POPDC1/2 and the vitamin D receptor, and regulates cell-cell adhesion stability required for normal cardiac morphology, conduction, and heart rhythm 1. XIRP1 also promotes skeletal muscle fiber recovery from injury and fatigue through regulation of satellite cell activation and survival. Pathogenic variants in XIRP1 cause diverse cardiac arrhythmias and cardiomyopathies. Rare variants have been identified in sudden unexplained nocturnal death syndrome and Brugada syndrome in Chinese Han populations 2, and XIRP1 mutations are implicated in arrhythmogenic right ventricular dysplasia and dilated cardiomyopathy 3, 4. In failing hearts, XIRP1 expression is downregulated, suggesting impaired intercalated disc stability contributes to disease progression. Notably, a neurogenetic disorder study identified XIRP1 mutations in consanguineous families affected by neurological disease 5. Recent evidence suggests XIRP1 also functions as a tumor suppressor: in glioblastoma, hypoxia-induced circRNAs suppress XIRP1 expression, promoting tumor aggressiveness, and lower XIRP1 correlates with higher glioma grade and worse prognosis 6.