WASHC2C (WASH complex subunit 2C) is a component of the pentameric WASH complex that plays a central role in endosomal cargo sorting and membrane trafficking. As a structural subunit, WASHC2C functions primarily in retrograde transport from endosomes to the trans-Golgi network (TGN) and in endosome-to-plasma membrane recycling 12. The protein interacts with retromer and sorting nexin proteins to mediate cargo selection and recycling of transmembrane receptors including GPCRs 3. WASHC2C contains multiple phosphoinositide-binding sites that facilitate endosomal localization and coordination with accessory factors like TBC1D23 45. Beyond canonical endosomal trafficking, WASHC2C participates in fluid-phase endocytosis pathways exploited by vaccinia virus for cell entry. Notably, genetic variation in WASHC2C is associated with differential activation of the mesolimbic reward system, particularly the ventral tegmental area and nucleus accumbens, suggesting roles in dopaminergic neurotransmission 6. Dysfunction of WASHC2C-dependent trafficking pathways has been implicated in pontocerebellar hypoplasia when associated proteins are mutated, indicating clinical relevance to neurological development 4. The WASH complex operates as a minimally concentrative coat protein complex adapted for bulk membrane trafficking rather than cargo concentration 5.