WASH complex subunit 4 (WASHC4)

WASH complex subunit 4 (WASHC4, also known as SWIP or KIAA1033) is an essential protein subunit of the pentameric WASH complex, which is necessary for the proper sorting and trafficking of proteins within endosomes[1][2]. Its main function is to stimulate localized actin polymerization by activating the Arp2/3 complex, which is crucial for the formation and fission of transport tubules from endosomes[1][2]. WASHC4 helps anchor the WASH complex to endosomal membranes by binding specific phosphoinositides (notably PI[3,5]P2), thereby regulating both retromer-dependent and retromer-independent endosomal sorting pathways[1]. It also interacts with endocytic adaptor and clathrin machinery proteins to couple endocytosis with membrane trafficking[1][2]. Mutations in WASHC4 destabilize the entire WASH complex, resulting in severe endo-lysosomal dysfunction, and have been linked to autosomal recessive intellectual developmental disorder (MRT43) and are implicated in neurodegenerative phenotypes in preclinical models[1][3][5]. There are currently no known drugs targeting WASHC4, and it is not considered a direct therapeutic target (such as a receptor or enzyme)[1].

Other names

KIAA1033SWIPStrumpellin and WASH-interacting proteinMRT43WASH complex subunit SWIPWASH complex subunit 7