WASHC4 (WASH complex subunit 4) is a core component of the WASH complex that functions as a nucleation-promoting factor at endosomal membranes 1. It recruits and activates the Arp2/3 complex to promote actin polymerization, facilitating the fission of tubular transport intermediates during endosome sorting 1. WASHC4 also interacts with VCP/p97 to regulate autophagy-mediated proteostasis, particularly in striated muscle 2. Recessive WASHC4 mutations cause autosomal recessive intellectual developmental disorder 43, characterized by moderate-to-mild intellectual disability, short stature, dysmorphic features, and macrocephaly 13. More recent evidence reveals broader neurological involvement: WASHC4 destabilization drives endo-lysosomal dysfunction leading to cognitive and progressive motor deficits in both mice and humans 4. Proteomic studies confirm dysregulation of neuromuscular-axis proteins and impaired skeletal muscle protein processing in affected patients 3. Genome-wide association studies identify WASHC4 variants associated with abnormalities of speech or vocalization in pediatric populations 5 and reward system reactivity in the ventral tegmental area and nucleus accumbens 6. These findings establish WASHC4 as essential for endosomal-lysosomal function with critical roles in neurodevelopment, motor function, and protein homeostasis across multiple tissues.