XIRP1 is an actin-binding protein essential for maintaining cardiac and skeletal muscle integrity. Its primary function is protecting actin filaments from depolymerization 1 and serving as a scaffolding protein at intercalated discs and myotendinous junctions. In cardiac tissue, XIRP1 localizes to intercalated discs where it interacts with POPDC1/2 and regulates cell-cell adhesion stability, maintaining normal cardiac morphology, electrical conductance, and heart rhythm 2. XIRP1 also acts as a 1,25D-modulated vitamin D receptor interacting protein that influences VDR-mediated transcription in a cell-specific manner 3. In skeletal muscle, XIRP1 regulates satellite cell activation and survival, promoting muscle fiber recovery from injury and fatigue. Deletion or mutation of XIRP1 causes late-onset cardiomyopathy with conduction defects 4. Genetic variants in XIRP1 are associated with sudden unexplained nocturnal death syndrome and Brugada syndrome 5, highlighting its critical role in cardiac electrical function. Additionally, XIRP1 expression is suppressed in glioblastoma through hypoxia-induced circRNA mechanisms, with lower XIRP1 levels correlating with higher tumor grade and worse prognosis 6. Novel associations link XIRP1 variants to adiponectin regulation in South Asian populations 7.