CAPZB (capping actin protein of muscle Z-line subunit beta) is an F-actin-capping protein that binds to the barbed ends of actin filaments in a calcium-independent manner, blocking subunit exchange without severing filaments [UniProt]. It plays critical roles in cytoskeletal organization and cell morphology regulation [UniProt]. CAPZB forms part of the dynactin complex, stabilizing its structure and facilitating dynein-mediated microtubule transport [UniProt]. Mechanistically, CAPZB restrains actomyosin contractility and regulates stress fiber dynamics; its loss increases myosin activity and tissue stiffness, leading to YAP/Hippo pathway activation 1. CAPZB is required for neural crest migration, cell differentiation, and proper craniofacial development, with both loss and overexpression causing developmental abnormalities 2. Clinically, CAPZB shows altered expression in multiple diseases: it is dysregulated in epithelioid sarcoma where it promotes cell growth and invasion 3, and is identified as a hub gene in ulcerative colitis, atherosclerosis, hypertrophic cardiomyopathy, and spinal cord injury pathogenesis 4567. In cancer, CAPZB functions downstream of ALIX to prevent F-actin accumulation around multivesicular bodies, facilitating exosome secretion that promotes tumor metastasis and immune evasion 8. These findings suggest CAPZB as a potential therapeutic target across multiple pathological contexts.