XIRP2 is a cardiac and sensory actin-binding protein that protects actin filaments from depolymerization 1. In cardiomyocytes, XIRP2 facilitates proper intercalated disk maturation and electrical conduction by promoting localization of adhesion molecules and interacting with cardiac ion channels Scn5a/Nav1.5 and Kcna5/Kv1.5, thereby supporting normal postnatal heart development and diastolic function. In the inner ear, XIRP2 maintains stereocilia morphology through organization of paracrystalline actin arrays in hair cells 1. Mechanistically, XIRP2 recruitment to damaged actin structures is force-dependent, mediated by a mechanosensor domain in its C-terminus, enabling repair of noise-induced stereocilial gaps through facilitation of monomeric actin enrichment 1. Clinically, XIRP2 dysregulation associates with cardiac stress responses; IL-11-induced heart failure involves stress-factor upregulation including Xirp2 2. XIRP2 downregulation occurs during vestibular hair cell ototoxicity 3, and mutations have been identified in neuroblastoma and collecting duct carcinoma patient cohorts 45. In cultured muscle, XIRP2 is significantly downregulated compared to tissue, correlating with muscle atrophy phenotypes 6.