RCSD1 (RCSD domain containing 1) is a cytoskeletal regulator that functions as a stress-responsive modulator of actin filament dynamics and cardiac development. Mechanistically, RCSD1 acts downstream of non-canonical Wnt11 signaling to regulate cardiac morphogenesis, ventricular trabeculation, and cardiomyocyte differentiation 1. The protein interacts with CapZ-binding partners and is involved in phosphorylation-dependent regulation of F-actin-capping protein activity, affecting actin filament assembly and cellular responses to osmotic stress. RCSD1 localizes to endosomal compartments and participates in retrograde transport and WASH complex-mediated protein trafficking. Disease relevance spans multiple contexts: RCSD1 mutations occur in hematological malignancies, particularly as RCSD1-ABL1 and RCSD1-ABL2 fusion genes associated with B-cell acute lymphoblastic leukemia (ALL), representing a high-risk subtype 234. In solid tumors, low RCSD1 expression correlates with poor prognosis and reduced immune infiltration in lung cancer and other malignancies 5. Clinically, RCSD1 genetic variants predict chemotherapy response in colorectal cancer 6, and RCSD1 serves as a diagnostic biomarker for hepatitis B-associated hepatocellular carcinoma 7. Additionally, reduced RCSD1 expression is associated with genetic predisposition to degenerative cervical myelopathy 8.