SHROOM4 is an actin-associated protein that functions as a regulator of cytoskeletal architecture, playing a critical role in embryonic development 1. The protein co-distributes with myosin II to distinct cytoplasmic F-actin structures and directly interacts with F-actin, modulating spatial organization of the actin cytoskeleton 1. SHROOM4 is expressed across multiple developing tissues, including neural tube, kidney epithelium, vascular endothelium, and urogenital systems 21. Pathogenic variants in SHROOM4 are associated with multiple neurodevelopmental and congenital disorders. Loss-of-function mutations cause X-linked intellectual disability and Stocco dos Santos syndrome 34. SHROOM4 disruption also causes congenital anomalies affecting the urinary tract, anorectal, cardiovascular, and central nervous systems 2. Zebrafish knockdown studies demonstrated pronephric cysts, cloacal anomalies, cardiac defects, and decreased ocular development, phenotypes rescued by wild-type SHROOM4 co-injection 2. Gene duplications in Xp11.22 are associated with intellectual disability, speech delay, early puberty, and skeletal abnormalities 56. SHROOM4 variants have been identified in autism spectrum disorder and Rett syndrome-like presentations 78. These findings establish SHROOM4 as a developmentally essential gene affecting multiple organ systems through cytoskeletal regulation.